治疗鸡大肠杆菌病的中药方剂筛选及其作用机理研究
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摘要
鸡大肠杆菌病(Chicken colibacillosis)是由某些血清型的致病性大肠埃希氏菌(Escherichia coli,简称大肠杆菌E.coli)所引起的传染病。各日龄的鸡均可发病,以雏鸡和中鸡居多。临床表现为多种症型,较常见的有败血症、肉芽肿、心包炎、肝周炎、气囊炎、肠炎、脐炎、全眼球炎、卵黄性腹膜炎、肿头综合征等,发病率为11%-69%,致死率为40.2%-90.3%,与其它病原混合感染时,死淘率会更高,其危害居细菌性疾病之首,常给养鸡业带来巨大经济的损失。
目前,鸡大肠杆菌病的防治还存在许多亟待解决的重大问题：一是致病性大肠杆菌血清型众多,我国现已报道的鸡致病性大肠杆菌血清型有60多种,现有的疫苗不能有效预防；二是养鸡场综合防控措施不够完善,为鸡致病性大肠杆菌的滋生和传播提供了外部条件；三是由于抗生素和化学抗菌药物的大量使用,导致病原产生了广泛的耐药性,使治疗效果不断下降,临床又不得不加大剂量并延长给药时间,大幅度提高了治疗难度与成本;四是抗生素和其他化学抗菌药在鸡肉、内脏和鸡蛋等产品中形成有害残留危害食品安全。
近年来,采用中药防治鸡大肠杆菌病的报道较多,且多数认为有较好效果。但尚存在下列问题：一是多数研究未从现代传染病学角度证明其有效性；二是未从现代药理学角度阐明其作用机理。为此,研究与开发更加安全、有效的中药制剂并阐明其作用机理将具有重要的理论研究与临床应用价值。
我们在中兽医药学理论指导下,根据相关文献报道,确定了清热类、祛湿类、理血类、理气类等114味中草药,以鸡大肠杆菌078作为目标菌株,进行了体外的抑菌试验,筛选出6种具有一定抗菌作用的中药,包括有芦荟、穿心莲、大蒜、锦灯笼、乌梅、石榴皮,其抑菌圈分别是15 mm、12 mm、12 mm、11 mm、11 mm、7 mm。运用硅胶柱层析、凝胶柱层析、ODS柱层析对芦荟的抗菌成分进行了分离、纯化,经过质谱、红外光谱和核磁共振分析了得到的抗菌单体物质,确定为延胡索酸。进一步的抗菌活性研究结果显示,延胡索酸对金黄色葡萄球、链球菌、大肠杆菌和沙门氏菌的MIC分别是50、50、780和780 gg/ml,MBC分别是100、100、1560和780μg/ml。
利用建立的人工感染鸡大肠杆菌病理模型,对39个备选方剂进行了筛选,发现方4、方5、方24与方26的效果较好,死亡率分别是30%、40%、26.7%、26.7%。为了进一步确证这些方剂的有效性,对方4、5、24、26进行了2次重复实验,结果显示4个方剂效果稳定,对实验性鸡大肠杆菌病均有治疗效果,死亡率在46.7%以下。相比之下,26号方效果最好,2次死亡率均为26.7%。通过正交试验对26号方组成药物的用量进行了筛选,确定其最佳配比为香附40g、穿心莲30 g、黄芪30 g,并将该方命名为“香芪汤”。
利用人工感染鸡大肠杆菌的病理模型,进一步考察了中药香芪汤的疗效。结果表明,中药香芪汤能改善感染大肠杆菌鸡只的饮水量和采食量。感染大肠杆菌鸡只的死亡率为50%,香芪汤中、高剂量能显著降低死亡率,分别是20%(P<0.05)和13.3%(P<0.01),且二组对感染鸡只的体增重也有较好的改善作用。血常规指标分析结果显示,攻毒对照组白细胞数极显著高于健康对照组(P<0.01),中药香芪汤能有效抑制血液白细胞过度的增加,低、中、高剂量组的白细胞数分别显著(P<0.05)和极显著(P<0.01)低于攻毒对照组：攻毒对照组的凝血细胞数显著低于健康对照组(P<0.05),高剂量的香芪汤能保护凝血细胞免受破坏,其数量显著高于攻毒对照组(P<0.05),香芪汤对红细胞也具有一定的保护作用；香芪汤能减轻接种大肠杆菌鸡只的病理变化,降低心包炎、肝周炎的发生率,并改善心、肝、脾、肾的脏体指数；通过ELISA法检测各组鸡只血清炎症介质TNF-α、IL-1和sEPCR的水平,结果显示,在相应的时间段内香芪汤能降低这些炎症介质的水平。以上结果表明,香芪汤对人工感染大肠杆菌鸡只具有良好的疗效.并且有可能是通过抗炎和抗凝血两条途径来发挥治疗作用的。
我们推测在鸡大肠杆菌致病过程中,微血管内皮细胞(Microvascular endothelial cells,MVECs起到了关键性的作用,因此,在本实验中,通过建立LPS诱导MVECs的炎症模型,考察了香芪汤及其有效成分对MVECs凝血途径相关因子的影响。MVECs长成融合状态的单层时,加入香芪汤、α-香附酮、黄芪甲苷和穿心莲内酯的低、中、高剂量作用细胞3h后,加入LPS刺激,18h收集培养细胞上清液,采用ELISA法测定PAI-1和TF的含量。结果,香芪汤和α-香附酮的低、中、高剂量组,黄芪甲苷中、高剂量组,穿心莲内酯低剂量组的PAI-1含量显著低于LPS对照组(P<0.05或P<0.01)；香芪汤低、中、高剂量组,α-香附酮中、高剂量组,黄芪甲苷高剂量组,穿心莲内酯高剂量组的TF含量显著低于LPS对照组(P<0.05或P<0.01),表明,香芪汤及其有效成分能抑制LPS诱导MVECs的PAI-1和TF的分泌,减轻凝血反应。
半定量RT-PCR结果显示,LPS作用MVECs 6 h后,能过多的提高PAI-1和TF基因mRNA表达的水平、降低上游调控基因KLF2 mRNA表达的水平。香芪汤组能降低PAI-1基因mRNA的表达水平,与LPS对照组比较差异显著(P<0.01),而穿心莲内酯组,黄芪甲苷和α-香附酮组的PAI-1基因mRNA表达水平与LPS对照组没有显著的差异(P>0.05)；香芪汤组和α-香附酮组的TF基因mRNA表达水平与LPS对照组比较差异极显著(P<0.01),黄芪甲苷、穿心莲内酯组的TF基因mRNA表达水平与LPS对照组比较差异不显著(P>0.05)。此外,香芪汤组、α-香附酮组、黄芪甲苷组和穿心莲内酯组的KLF2基因mRNA表达水平与LPS对照组比较差异显著(P<0.01)。以上结果表明,香芪汤及其有效成分能够一定程度上抑制LPS诱导的MVECs PAI-1和TF基因mRNA水平的影响,并且对这两个基因的上游调控基因KLF2也有一定的调节作用。
利用Western blot方法检测了香芪汤及其有效成分对MVECs分泌TNF-α和表达ICAM-1蛋白以及上游调控蛋白IκB-α、NF-κB p65的影响。结果显示,香芪汤和α-香附酮的低、中、高剂量组,黄芪甲苷的高剂量组,穿心莲内酯中、高剂量组均能极显著降低LPS诱导的MVECs TNF-α的分泌量(P<0.01)；香芪汤、α-香附酮、黄芪甲苷、穿心莲内酯能降低ICAM-1蛋白的表达量,与LPS对照组相比差异极显著(P<0.01),以上结果表明香芪汤及其有效成分具有较好的抗炎作用。另外,香芪汤及其有效成分不能抑制LPS诱导的MVECs IκB-α蛋白表达量的下降,能够抑制NF-κB p65蛋白表达量的增加,表明,香芪汤及其有效成分的抗炎作用是通过抑制NF-κB p65来介导的。
综上所述,本课题利用体外抑菌试验对114味中药进行了筛选,利用人工感染鸡大肠杆菌的病理模型对39个中药复方进行了筛选,得到一个效果最好的中药复方,命名为香芪汤。通过进一步的疗效观察,证明香芪汤对感染鸡只的饮水量、采食量、死亡率、体增重、血液学指标、典型病理变化、脏体指数以及血清炎症介质水平等指标具有良好的改善作用。香芪汤的疗效可能是通过调节KLF2介导的凝血反应和NF-κB介导的炎症反应来完成的。
Chicken colibacillosis. which is caused by avian pathogenic Escherichia coli (APEC), is one of the most significant and widespread infectious diseases occurring in different varieties and age of chicken. It is responsible for large financial losses for the poultry industry each year due to high morbility and mortality. It is also a deuteropathy of New castle disease. avian influenza and other chronic respiratory disease. Antibacterial agents. and inactivated and subunit vaccines are applied to curing or preventing this disease at present. However. the vaccines and antibacterial agents are often invalid due to the variform serotypes of APEC and complicated pathogenic mechanisms. In addition. because of the unreasonable usage of antibacterial agents for long time. the human food security and public health problem are caused. The traditional Chinese medicine has lots of advantages in curative effect. security. and controlling drug resistance and residue. so it is more important for prevention and treatment of livestock infectious disease. Therefore. in this study, we had screened an effective Chinese medical formula through a serial of experiments in vitro and in vivo, then further observed its curative effect and studied its action mechanism from cellular and molecular perspectives. According to these, we hoped to provide a theoretical basis for further research on this Chinese medical formula and the application in prevention or therapy for chicken colibacillosis.
According to pertinent literature, we chose 114 kinds of Chinese materia medica including heat-clearing drugs, dampness-eliminating drugs. blood-regulating drugs and others to examine their antibacterial activity against APEC through bacteriostasis test in vitro.6 kinds of Chinese material medica had good antibacterial activity. such as aloe. andrographitis. garlic. calyx seu fructus physalis. fructus mume and granati cortex. Their inhibition zone were respectively 15.12.12.11.11 and 7 mm. Then, we isolated and purified the antibacterial components of aloe by silica gel column chromatography, gel column chromatography and ODS column chromatography. At last, the antibacterial component was identified as fumaric acid through MS. IR and NMR analysis. Then, we further studied the activity of fumaric acid against Escherichia coli. Staphylococcus aureus, Streptococcus. Salmonella. The MIC was respectively 50,50,780 and 780μg/ml and MBC was respectively 100.100,1560 and 780μg/ml.
We had screened 39 Chinese medical formula through chicken model infected by APEC. The results showed that No.4. No.5. No.24 and NO.26 had better effect on decreasing mortality. and their mortality were respectively 30%.40%.26.7%. 26.7%. To confirm the effects of these Chinese medical formula. we carried out 2 repeated tests and found that they had stable effects on chicken infected APEC. the mortality were below 46.7%. And No.26 is the best one which the mortality was 26.7% in 2 repeated tests. Then we defined the usage of the combined drugs of No.26. that is Rhizoma Cyperi 40 g. Andrographis paniculata 30 g. Astragalus membranaceus 30 g. and designated it as "Xiang-Qi-Tang"
We had further detected the effects of XQT using chicken model infected by APEC. The results showed that XQT could improve food intake and water consumption of infected chicken. The mortality of APEC group was 50%. the middle dose group and high dose group of XQT were respectively 20%(P<0.05) and 13.3% (P<0.01). and the two XQT groups also could improve weight gain. The blood routine results showed that the WBC of APEC group were significantly higher than that of control group (P<0.01). the WBC of low. middle and high dose group of XQT were significantly lower than that of APEC group (P<0.05 or P<0.01):the number of thrombocyte of APEC were significantly lower than that of control group (P<0.05). and the number of high dose group of XQT were higher than that of APEC group (P<0.05):XQT also could protect red blood cell. Then. XQT could decrease the typical pathological change of infected chicken, including decreasing incidence of pericarditis and perihepatitis and improving organ indexes of heart, liver, spleen and kidney. Through ELISA method, we detected the levels of TNF-a. IL-1 and sEPCR in serum of infected chicken, the results showed that XQT could decrease these inflammation mediator. These results indicated that XQT had better effect on chicken infected by APEC. which might be through anti-inflammation and anti-coagulation to play its role.
Microvascular endothelial cells play an important role in pathogenic process of APEC. Therefore, in this study, we detected the effects of XQT and its active components on coagulation. through the inflammation model of MVECs induced by LPS. MVECs was treated with XQT and its active components for 3h. then challenged with 1μg/mL LPS. the cells were incubated at 37℃in a cell incubator for 18h. The supernatants were collected and analyzed the contents of PAI-1 and TF by ELISA kits. The results showed that as compared with LPS control group, the PAI-1 contents were significantly decreased in the low. middle and high dose group of XQT andα-Cyperone. in the middle and high dose group of AstragalosideⅣ, and in the low dose Andrographolide;the TF contents were significantly decreased in the low. middle and high dose group of XQT. in the middle and high dose group ofα-Cyperone. and in the high dose group of AstragalosideⅣand Andrographolide. It suggested that XQT and its active components could inhibite the secretion of PAI-1 and TF, which could decrease coagulation.
We analyzed effect of XQT and its active components on mRNA levels of PAI-1, TF and KLF2 using semi-quantitive RT-PCR. The results showed that, after MVECs challenged with LPS for 6h. as compared with LPS control group. the levels of PAI-1 mRNA significantly decreased in XQT group. while the levels did not decrease inα-Cyperone. AstragalosideⅣand Andrographolide group; the levels of TF mRNA significantly decreased in XQT andα-Cyperone group. while the levels did not decrease in AstragalosideⅣand Andrographolide group:the levels of KLF2 mRNA significantly decreased in XQT.α-Cyperone. AstragalosideⅣ. Andrographolide group. These results suggested that XQT and its active components could inhibit the levels of mRNA of PAI-1 and TF induced bv LPS. and regulated the levels of mRNA of KLF2 which was the regulator of PAI-1 and TF.
We analyzed effect of XQT and its active components on expression of ICAM-1, IκB-αand NF-κB p65 using ELISA and western blot. The results showed that as compared with LPS control group. the levels of mRNA TNF-a significantly decreased in low, middle and high dose group of XQT and a-Cyperone. in middle and high dose group of Astragaloside IV and Andrographolide. The expression of ICAM-1 protein significantly decreased in XQT. a-Cyperone. Astragaloside IV and Andrographolide. These results suggested that XQT and its active components had better anti-inflammation. In addition. XQT and its active components did not increase the expression of IκB-α. while they could decrease the expression of NF-κB p65. It suggested that the anti-inflammation action of XQT and its active components was mediated by decreasing the expression of NF-κB p65.
Based on all the information above, we obtained an effective Chinese medical formula. XQT. curing chicken colibacillosis through in vitro and in vivo screening. XQT could improve water consumption. food intake, mortality, weight gain. blood routine. typical pathological change. organ indexes and inflammation mediator. And the effect of XQT might be performed through regulating the coagulation mediated by KLF2 and inflammation mediated by NF-κB.
目前,鸡大肠杆菌病的防治还存在许多亟待解决的重大问题：一是致病性大肠杆菌血清型众多,我国现已报道的鸡致病性大肠杆菌血清型有60多种,现有的疫苗不能有效预防；二是养鸡场综合防控措施不够完善,为鸡致病性大肠杆菌的滋生和传播提供了外部条件；三是由于抗生素和化学抗菌药物的大量使用,导致病原产生了广泛的耐药性,使治疗效果不断下降,临床又不得不加大剂量并延长给药时间,大幅度提高了治疗难度与成本;四是抗生素和其他化学抗菌药在鸡肉、内脏和鸡蛋等产品中形成有害残留危害食品安全。
近年来,采用中药防治鸡大肠杆菌病的报道较多,且多数认为有较好效果。但尚存在下列问题：一是多数研究未从现代传染病学角度证明其有效性；二是未从现代药理学角度阐明其作用机理。为此,研究与开发更加安全、有效的中药制剂并阐明其作用机理将具有重要的理论研究与临床应用价值。
我们在中兽医药学理论指导下,根据相关文献报道,确定了清热类、祛湿类、理血类、理气类等114味中草药,以鸡大肠杆菌078作为目标菌株,进行了体外的抑菌试验,筛选出6种具有一定抗菌作用的中药,包括有芦荟、穿心莲、大蒜、锦灯笼、乌梅、石榴皮,其抑菌圈分别是15 mm、12 mm、12 mm、11 mm、11 mm、7 mm。运用硅胶柱层析、凝胶柱层析、ODS柱层析对芦荟的抗菌成分进行了分离、纯化,经过质谱、红外光谱和核磁共振分析了得到的抗菌单体物质,确定为延胡索酸。进一步的抗菌活性研究结果显示,延胡索酸对金黄色葡萄球、链球菌、大肠杆菌和沙门氏菌的MIC分别是50、50、780和780 gg/ml,MBC分别是100、100、1560和780μg/ml。
利用建立的人工感染鸡大肠杆菌病理模型,对39个备选方剂进行了筛选,发现方4、方5、方24与方26的效果较好,死亡率分别是30%、40%、26.7%、26.7%。为了进一步确证这些方剂的有效性,对方4、5、24、26进行了2次重复实验,结果显示4个方剂效果稳定,对实验性鸡大肠杆菌病均有治疗效果,死亡率在46.7%以下。相比之下,26号方效果最好,2次死亡率均为26.7%。通过正交试验对26号方组成药物的用量进行了筛选,确定其最佳配比为香附40g、穿心莲30 g、黄芪30 g,并将该方命名为“香芪汤”。
利用人工感染鸡大肠杆菌的病理模型,进一步考察了中药香芪汤的疗效。结果表明,中药香芪汤能改善感染大肠杆菌鸡只的饮水量和采食量。感染大肠杆菌鸡只的死亡率为50%,香芪汤中、高剂量能显著降低死亡率,分别是20%(P<0.05)和13.3%(P<0.01),且二组对感染鸡只的体增重也有较好的改善作用。血常规指标分析结果显示,攻毒对照组白细胞数极显著高于健康对照组(P<0.01),中药香芪汤能有效抑制血液白细胞过度的增加,低、中、高剂量组的白细胞数分别显著(P<0.05)和极显著(P<0.01)低于攻毒对照组：攻毒对照组的凝血细胞数显著低于健康对照组(P<0.05),高剂量的香芪汤能保护凝血细胞免受破坏,其数量显著高于攻毒对照组(P<0.05),香芪汤对红细胞也具有一定的保护作用；香芪汤能减轻接种大肠杆菌鸡只的病理变化,降低心包炎、肝周炎的发生率,并改善心、肝、脾、肾的脏体指数；通过ELISA法检测各组鸡只血清炎症介质TNF-α、IL-1和sEPCR的水平,结果显示,在相应的时间段内香芪汤能降低这些炎症介质的水平。以上结果表明,香芪汤对人工感染大肠杆菌鸡只具有良好的疗效.并且有可能是通过抗炎和抗凝血两条途径来发挥治疗作用的。
我们推测在鸡大肠杆菌致病过程中,微血管内皮细胞(Microvascular endothelial cells,MVECs起到了关键性的作用,因此,在本实验中,通过建立LPS诱导MVECs的炎症模型,考察了香芪汤及其有效成分对MVECs凝血途径相关因子的影响。MVECs长成融合状态的单层时,加入香芪汤、α-香附酮、黄芪甲苷和穿心莲内酯的低、中、高剂量作用细胞3h后,加入LPS刺激,18h收集培养细胞上清液,采用ELISA法测定PAI-1和TF的含量。结果,香芪汤和α-香附酮的低、中、高剂量组,黄芪甲苷中、高剂量组,穿心莲内酯低剂量组的PAI-1含量显著低于LPS对照组(P<0.05或P<0.01)；香芪汤低、中、高剂量组,α-香附酮中、高剂量组,黄芪甲苷高剂量组,穿心莲内酯高剂量组的TF含量显著低于LPS对照组(P<0.05或P<0.01),表明,香芪汤及其有效成分能抑制LPS诱导MVECs的PAI-1和TF的分泌,减轻凝血反应。
半定量RT-PCR结果显示,LPS作用MVECs 6 h后,能过多的提高PAI-1和TF基因mRNA表达的水平、降低上游调控基因KLF2 mRNA表达的水平。香芪汤组能降低PAI-1基因mRNA的表达水平,与LPS对照组比较差异显著(P<0.01),而穿心莲内酯组,黄芪甲苷和α-香附酮组的PAI-1基因mRNA表达水平与LPS对照组没有显著的差异(P>0.05)；香芪汤组和α-香附酮组的TF基因mRNA表达水平与LPS对照组比较差异极显著(P<0.01),黄芪甲苷、穿心莲内酯组的TF基因mRNA表达水平与LPS对照组比较差异不显著(P>0.05)。此外,香芪汤组、α-香附酮组、黄芪甲苷组和穿心莲内酯组的KLF2基因mRNA表达水平与LPS对照组比较差异显著(P<0.01)。以上结果表明,香芪汤及其有效成分能够一定程度上抑制LPS诱导的MVECs PAI-1和TF基因mRNA水平的影响,并且对这两个基因的上游调控基因KLF2也有一定的调节作用。
利用Western blot方法检测了香芪汤及其有效成分对MVECs分泌TNF-α和表达ICAM-1蛋白以及上游调控蛋白IκB-α、NF-κB p65的影响。结果显示,香芪汤和α-香附酮的低、中、高剂量组,黄芪甲苷的高剂量组,穿心莲内酯中、高剂量组均能极显著降低LPS诱导的MVECs TNF-α的分泌量(P<0.01)；香芪汤、α-香附酮、黄芪甲苷、穿心莲内酯能降低ICAM-1蛋白的表达量,与LPS对照组相比差异极显著(P<0.01),以上结果表明香芪汤及其有效成分具有较好的抗炎作用。另外,香芪汤及其有效成分不能抑制LPS诱导的MVECs IκB-α蛋白表达量的下降,能够抑制NF-κB p65蛋白表达量的增加,表明,香芪汤及其有效成分的抗炎作用是通过抑制NF-κB p65来介导的。
综上所述,本课题利用体外抑菌试验对114味中药进行了筛选,利用人工感染鸡大肠杆菌的病理模型对39个中药复方进行了筛选,得到一个效果最好的中药复方,命名为香芪汤。通过进一步的疗效观察,证明香芪汤对感染鸡只的饮水量、采食量、死亡率、体增重、血液学指标、典型病理变化、脏体指数以及血清炎症介质水平等指标具有良好的改善作用。香芪汤的疗效可能是通过调节KLF2介导的凝血反应和NF-κB介导的炎症反应来完成的。
Chicken colibacillosis. which is caused by avian pathogenic Escherichia coli (APEC), is one of the most significant and widespread infectious diseases occurring in different varieties and age of chicken. It is responsible for large financial losses for the poultry industry each year due to high morbility and mortality. It is also a deuteropathy of New castle disease. avian influenza and other chronic respiratory disease. Antibacterial agents. and inactivated and subunit vaccines are applied to curing or preventing this disease at present. However. the vaccines and antibacterial agents are often invalid due to the variform serotypes of APEC and complicated pathogenic mechanisms. In addition. because of the unreasonable usage of antibacterial agents for long time. the human food security and public health problem are caused. The traditional Chinese medicine has lots of advantages in curative effect. security. and controlling drug resistance and residue. so it is more important for prevention and treatment of livestock infectious disease. Therefore. in this study, we had screened an effective Chinese medical formula through a serial of experiments in vitro and in vivo, then further observed its curative effect and studied its action mechanism from cellular and molecular perspectives. According to these, we hoped to provide a theoretical basis for further research on this Chinese medical formula and the application in prevention or therapy for chicken colibacillosis.
According to pertinent literature, we chose 114 kinds of Chinese materia medica including heat-clearing drugs, dampness-eliminating drugs. blood-regulating drugs and others to examine their antibacterial activity against APEC through bacteriostasis test in vitro.6 kinds of Chinese material medica had good antibacterial activity. such as aloe. andrographitis. garlic. calyx seu fructus physalis. fructus mume and granati cortex. Their inhibition zone were respectively 15.12.12.11.11 and 7 mm. Then, we isolated and purified the antibacterial components of aloe by silica gel column chromatography, gel column chromatography and ODS column chromatography. At last, the antibacterial component was identified as fumaric acid through MS. IR and NMR analysis. Then, we further studied the activity of fumaric acid against Escherichia coli. Staphylococcus aureus, Streptococcus. Salmonella. The MIC was respectively 50,50,780 and 780μg/ml and MBC was respectively 100.100,1560 and 780μg/ml.
We had screened 39 Chinese medical formula through chicken model infected by APEC. The results showed that No.4. No.5. No.24 and NO.26 had better effect on decreasing mortality. and their mortality were respectively 30%.40%.26.7%. 26.7%. To confirm the effects of these Chinese medical formula. we carried out 2 repeated tests and found that they had stable effects on chicken infected APEC. the mortality were below 46.7%. And No.26 is the best one which the mortality was 26.7% in 2 repeated tests. Then we defined the usage of the combined drugs of No.26. that is Rhizoma Cyperi 40 g. Andrographis paniculata 30 g. Astragalus membranaceus 30 g. and designated it as "Xiang-Qi-Tang"
We had further detected the effects of XQT using chicken model infected by APEC. The results showed that XQT could improve food intake and water consumption of infected chicken. The mortality of APEC group was 50%. the middle dose group and high dose group of XQT were respectively 20%(P<0.05) and 13.3% (P<0.01). and the two XQT groups also could improve weight gain. The blood routine results showed that the WBC of APEC group were significantly higher than that of control group (P<0.01). the WBC of low. middle and high dose group of XQT were significantly lower than that of APEC group (P<0.05 or P<0.01):the number of thrombocyte of APEC were significantly lower than that of control group (P<0.05). and the number of high dose group of XQT were higher than that of APEC group (P<0.05):XQT also could protect red blood cell. Then. XQT could decrease the typical pathological change of infected chicken, including decreasing incidence of pericarditis and perihepatitis and improving organ indexes of heart, liver, spleen and kidney. Through ELISA method, we detected the levels of TNF-a. IL-1 and sEPCR in serum of infected chicken, the results showed that XQT could decrease these inflammation mediator. These results indicated that XQT had better effect on chicken infected by APEC. which might be through anti-inflammation and anti-coagulation to play its role.
Microvascular endothelial cells play an important role in pathogenic process of APEC. Therefore, in this study, we detected the effects of XQT and its active components on coagulation. through the inflammation model of MVECs induced by LPS. MVECs was treated with XQT and its active components for 3h. then challenged with 1μg/mL LPS. the cells were incubated at 37℃in a cell incubator for 18h. The supernatants were collected and analyzed the contents of PAI-1 and TF by ELISA kits. The results showed that as compared with LPS control group, the PAI-1 contents were significantly decreased in the low. middle and high dose group of XQT andα-Cyperone. in the middle and high dose group of AstragalosideⅣ, and in the low dose Andrographolide;the TF contents were significantly decreased in the low. middle and high dose group of XQT. in the middle and high dose group ofα-Cyperone. and in the high dose group of AstragalosideⅣand Andrographolide. It suggested that XQT and its active components could inhibite the secretion of PAI-1 and TF, which could decrease coagulation.
We analyzed effect of XQT and its active components on mRNA levels of PAI-1, TF and KLF2 using semi-quantitive RT-PCR. The results showed that, after MVECs challenged with LPS for 6h. as compared with LPS control group. the levels of PAI-1 mRNA significantly decreased in XQT group. while the levels did not decrease inα-Cyperone. AstragalosideⅣand Andrographolide group; the levels of TF mRNA significantly decreased in XQT andα-Cyperone group. while the levels did not decrease in AstragalosideⅣand Andrographolide group:the levels of KLF2 mRNA significantly decreased in XQT.α-Cyperone. AstragalosideⅣ. Andrographolide group. These results suggested that XQT and its active components could inhibit the levels of mRNA of PAI-1 and TF induced bv LPS. and regulated the levels of mRNA of KLF2 which was the regulator of PAI-1 and TF.
We analyzed effect of XQT and its active components on expression of ICAM-1, IκB-αand NF-κB p65 using ELISA and western blot. The results showed that as compared with LPS control group. the levels of mRNA TNF-a significantly decreased in low, middle and high dose group of XQT and a-Cyperone. in middle and high dose group of Astragaloside IV and Andrographolide. The expression of ICAM-1 protein significantly decreased in XQT. a-Cyperone. Astragaloside IV and Andrographolide. These results suggested that XQT and its active components had better anti-inflammation. In addition. XQT and its active components did not increase the expression of IκB-α. while they could decrease the expression of NF-κB p65. It suggested that the anti-inflammation action of XQT and its active components was mediated by decreasing the expression of NF-κB p65.
Based on all the information above, we obtained an effective Chinese medical formula. XQT. curing chicken colibacillosis through in vitro and in vivo screening. XQT could improve water consumption. food intake, mortality, weight gain. blood routine. typical pathological change. organ indexes and inflammation mediator. And the effect of XQT might be performed through regulating the coagulation mediated by KLF2 and inflammation mediated by NF-κB.
引文
[1]甘孟侯.中国禽病学[M].北京：中国农业出版社,1999：169
[2]Otaki Y.Poultry disease control programme in Japan[J].Asian Livestock,1995, 20:65-67
[3]史喜菊,郑明学,冯梁.鸡大肠杆菌病最新研究进展[J].畜禽业,2000,174(8)：14-16
[4]陆承平主编.兽医微生物学(第三版)[M].北京：中国农业出版社,2001：215-223
[5]韩文瑜,何昭阳,刘玉斌主编.病原细菌检验技术[M].吉林科学技术出版社,1992：270-271
[6]Yaguchi K, Ogitani T, Osawa R, et al. Virulence factors of avian pathogenic Escherichia coli strains isolated from chickens with colisepticemia in Japan[J]. Avian Dis,2007,51(3):656-62
[7]Chart H, Smith HR, La Ragione, et al. An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5α and EQ1 [J]. J. Appl. Microbiol,2000,89:1048-1058
[8]恽时锋,潘震寰,郑明球.鸡大肠杆菌病研究进展[J].畜牧与兽医,1998,30(6)：277-280
[9]蔡宝祥.家畜传染病学(第四版)[M]..北京：中国农业出版社,2001
[10]夏业才,潘松年.禽大肠杆菌病的研究鸡致病性大肠杆菌的血清型鉴定[J].中国兽药杂志,1991,25(4)：1-2
[11]林维庆.鸡大肠杆菌病[J].华南农业大学学报,1991,12(3)：7-13
[12]王晶钰,张国祥,王英珍,等.陕西省鸡致病性大肠杆菌的分离及血清型鉴定和药敏试验[J].中国兽医科技,1996,26(3)：15-17
[13]陈绍熙,梁国芳,郭强,等.鸡大肠杆菌病病原分离鉴定和多价蜂胶灭活苗的研制[J].中国畜禽传染病,1997,2：22-25
[14]周继宏,朱国强,庄国宏,等.鸡致病性大肠杆菌的分离与鉴定[J].中匡 畜禽传染病,1997,19(6)：27-28
[15]邵华斌,杨峻,黎秋花,等.湖北省鸡大肠杆菌病流行情况调查及病原分离鉴定[J].中国兽医科技,1998,28(9)：14-15
[16]高轩,李潭清.河北省禽病原性大肠杆菌的血清型鉴定[J].河北农业大学学报,1998,21(1)：56-59
[17]李玉文,李惠兰,齐景文,等.辽宁省禽大肠埃希氏菌血清型的调查及其致病性试验[J].中国兽医科学,2006,36(8)：630-633
[18]丁伯良,鄢明华,王英珍,等.天津地区鸡致病性大肠杆菌血清型分布及其优势血清型的外膜蛋白型研究[J].动物医学研究进展,2003.24(2)：94-96
[19]刘远飞,曹翠萍,宁海强,等.山东省鸡大肠杆菌血清型分布及耐药性分析[J].家畜生态学报,2008,29(1)：88-90
[20]魏麟,黎晓英,刘胜贵,等.湖南西部地区鸡大肠杆菌血清型分布及耐药性分析[J].安徽农业科学,2009,37(28)：13615-13617
[21]戴鼎震,恽时锋.鸡源性大肠杆菌菌毛研究进展[J].湖北农学院学报.1999.19(4)：371
[22]Weiser JN, Gotschlich EC. Outer membrane protein A (OmpA) contributes to serum resistance and pathogenicity of Escherichia coli K-1 [J]. Infect immune. 1991,59(7):2252-2258
[23]NolanLK, Wooley R E, Cooper PK, et al. Transposon mutagenesis used to study the role of complement resistnace in the vimlence of an vaian Eseherichia coli isolate[J]. Avian Disease,1992,36:398-400
[24]LeeMn, Wooley R E, Brown J, et al. Comparison of aquantitative microtiter method aquantitative automated method and the plate-count method for detemrining mierobial complement resistnaee[J]. Avina Diseasa,1991,35: 892
[25]陈红玲,何芳,朱兴全,等.鸡大肠杆菌病及其防治[J].广东畜牧兽医科技,2003,28(3)：30-33
[26]彭德旺,葛兆宏,王涛,等.养鸡技术讲座[J].甘肃畜牧兽医.1995,124(5):32-35
[27]陈静,王贵升,田夫林,等.山东省鸡大肠杆菌和沙门氏菌的发病趋势和耐药性变化分析[J].中国兽医杂志,2006,40(2)：19-22
[28]钟映梅,刘宏雨,孙刚,等.应用试剂条对大肠杆菌病的诊断与防制[M].第15届世界禽病大会论文集,2007：165
[29]于金玲,刘孝刚,张书杰,等。产蛋鸡传染性喉气管炎与大肠杆菌病混合感染的诊治[J].辽宁畜牧兽医,2003,5：18
[30]甘孟候.中国禽病学[M].北京：中国农业出版社,1999,168-174
[31]Deb JR et al. Lab.Trials with inactivated vaccines against E.coli (O78:K80) infection in fowls [J]. Res Vet Sci,1976,20:131-138
[32]Panigrahy B. Immunogenic potency of an oil-emulsified E.coli bacterin [J]. Avian Diseases,1983,27(2):475-481
[33]Morley A J. Swollen-head syndrome in broiler chickens [J]. Avian Diseases, 1984,28(1):238-243
[34]梁国芳,陈绍熙,郭强,等.鸡大肠杆菌多价蜂胶灭活苗的研制[J].中国畜禽传染病,1997,19(6)：37-39
[35]杨峻,邵华斌,刘泽文,等.鸡大肠杆菌病多价蜂胶灭活疫苗的研究[J].湖北畜牧兽医,1999,3：9-13
[36]张安国,沈华,马文芝,等.鸡大肠埃希氏菌多价油乳剂灭活苗的研制[J].中国兽医科技,1998,28(7)：6-8
[37]崔锦鹏,颜世敢,徐培莲,等.鸡大肠杆菌多价油乳剂灭活疫苗的研制及应用[J].山东农业科学,2000,6：45-47
[38]杨小燕,沈绍新,李晓华,等.鸡致病性大肠杆菌的分离鉴定和自场灭活苗的研制[J].中国兽医杂志,1999,25(2)：23-24
[39]窦大庆,彩尼瓦尔,古丽巴哈尔,等.喀什地区鸡大肠杆菌的分离鉴定及多价灭活苗的研制[J].中国兽医杂志,2002.38(3)：19-20
[40]杨发龙.禽大肠杆菌病疫苗[J].西南民族学院学报自然科学版,2000,26(4)：422-424
[41]Gyimah J E. Immunogenicity of an Escherichia coli multivalent pilus vaccine in chickens [J]. Avian Dis,1986,30:687-689
[42]英特威.鸡大肠杆菌病及其防制[J].养禽与禽病防制,1995,11：25-26
[43]戴鼎震,李康然.禽大肠杆菌菌毛的特性及免疫原性研究[J].广西农学院学报,1992,11(2)：47-54
[44]黄淑坚,林维庆,李进红.鸡病原性大肠杆菌荚膜多糖亚单位疫苗的研究[J].中国兽医科技,1996,22(6)：50-51
[45]Korn A, Rajabi Z, Wassum B, et al. Enhancement of uptake of lipopolysaccharide in macrophages by the major outer membrane protein OmpA of Gram-negative bacteria[J]. Infect Immun,1995,63(7):2697-2705
[46]Wiertz E J, Delvig E M, Donders, et al. T-cell responses to outer membrane proteins of Neisseria meningitidis:comparative study of the opa.opc and por A proteins[J]. Infect Immun,1996,64(1):298-304
[47]赵香汝.禽大肠杆菌外膜蛋白免疫原性的研究[D].北京：北京农业大学,1998
[48]刘熙文,黄青云.禽大肠杆菌病4种弱毒菌苗免疫原性的研究[J].中国兽医杂志,1999,25(3)：21-14
[49]Frommer A, Freidlin P J, Brod R R. Experimental vaccination of young chickens with a live non-pathogenic strain of Escherichia coli[J]. Avian Pathol, 1994,23(3):425-433
[50]Abdul-Aziz T A, El-Aukhon S N. Serum sensitivity and pathogenicity for chickens and chicks embrys of Escherichia coli JS strain [J]. Vet Res,1996, 27(3):267-271
[51]Yang H C, ChenS, David G W, et al. Characterization of multiple antimicrobial resistant Escherichia coli isolates from diseased chickens and swine in China [J]. Journal of Clinical Microbiology,2004,42(8):3483-3489
[52]Murray B E. New aspects of antimicrobial resistance and resulting the therapeutic dilemmas[J]. J Infect Dis,1991,163:1185
[53]雷连成.细菌的耐药性(Ⅰ)[J].中国兽药杂志,2002,36(11)：41-44.49
[54]崔晓文,张秀英.细菌耐药性产生的分子机制与耐药基因的快速检测方法[J].中国兽药杂志,2004,38(9)：30-32
[55]沈关心.微生物学与免疫学(第5版)[M].北京：人民卫生出版社,2003,288
[56]张永利,万献尧.细菌耐药性研究进展[J].中国医师杂志,2004,6(12)：1721-1722
[57]Maneewannakul K, Levy SB. Identification for mar mutants among quinoloneresistant clinical isolates of Escherichia coli[J]. Antimicroh Agents Chemother,1996,40(7):1695-1698
[58]Mobak KDL, Baggesen FK, Aarestrup JM, et al. An outbreak of multi-drug-resistant, quinolone-resistant Salmonella enterica serotype Ty-phimurium DT104[J]. Engl Med,1999,341:1420-1425
[59]Davies J, Smith DI. Plasmid-determined resistance to antimicrobiala-gents [J]. Annd Rev Microbiol,1978,32:469-518
[60]Dorthe S, Frank MA, Lars BJ. Characterization of integrons and antibiotic resistance genes in Danish multiresistants Salmonella enterica Ty-Phimurium DT104[J]. FEMS Microbiology Letters,1998,160:37-41
[61]P Mazodier, R Petter, C Thompson. Intergeneric conjugation between E. coli and Steptomyces species [J]. J Bacteria,1989,171(6):3583-3585
[62]Farrar W E. Molecular analysis of plasmids in epidemiologic investigation [J]. J Infect Dis,1983,148(1):1
[63]P Mazodier, J Davies. Gene transfer between distantly related bacteria [J]. Annu Rev Genetics,1991,25:147-171
[64]张秀英.抗生素的耐药机制分类及概述[A].1999年中国兽医微生物学学术年会论文集[C].北京：中国微生物学会兽医微生物学专业委员会,1999：205-209
[65]张继瑜,赵荣材,邓旭明,等.喹诺酮类药物耐药性的分子机制[A].中国畜牧兽医学会—兽医药理毒理学分会第七次学术讨论会论文摘要汇编[C].北京：中国畜牧兽医学会.2000,15
[66]雷连成,韩文瑜.段艳.大肠杆菌耐药性抑制剂作用机制的初步研究[J],中国兽药杂志,2004.38(2)：18-21
[67]张永利.细菌耐药性研究进展[J].中国医师杂志,2004,6(12)：1721-1722
[68]朱力军.动物大肠杆菌耐药性的变化趋势[J].中国兽药杂志,2001,35(2)： 16-18
[69]vanden Bogaard A E, London N, Driessen C, et al. Antibiotic resistance of faecal Escherichia coli in poultry farmers and poultry slaughterers [J]. Journal of Antimicrobial Chemotherapy,2001,47:763-771
[70]柳春华,韩少礼,吕学章,等.从药敏试验的结果观察鸡大肠杆菌病的耐药性[J].黑龙江畜牧兽医,1993,11：25-26
[71]高崧,崔国搁,唐一鸣,等.我国部分地区105个禽大肠杆菌的药敏试验[J].中国畜禽传染病,1998,20(5)：300-301
[72]孙鎏国,蒋锁俊,姚德法.致病性大肠杆菌的耐药性监测[J].上海畜牧兽医通讯,2004,5：18
[73]刘栓江,杨汉春,王建肪,等.鸡源大肠杆菌的耐药性监测[J].中国兽医杂志,2004,40(6)：48-49
[74]孙海虹,马同锁,于珊,等.鸡大肠杆菌的菌株鉴定及药物敏感试验[J].河北师范大学学报(自然科学版),2005,29(6)：263-266
[75][76]雷连成,韩文瑜,郑丹.大肠杆菌流行株耐药特性对其免疫效果的影响[J].吉林农业大学学报,2005,27(5)：554-558
[76]王红宁.禽病的新特点及其防治对策和用药安全[J].中国畜牧杂志,2007,43(16)：12-15
[77]李桂喜.鸡大肠埃希氏菌血清型鉴定及药敏试验研究[J].第15届世界禽病大会论文集,2007,167
[78]潘渭涓,陈祥,王晓泉,等.1993-2008年禽源大肠杆菌和沙门菌对喹诺酮类药物耐药性分析[J].中国人兽共患病学报,2009,25(7)：630
[79]Prats G, Mirelis B, Llovet T, et al. Antibiotic resistance trends in enteropathogenic bacterial solated in 1985～1987 and 1995～1998 in Barcelona [J]. Antimicrob Agents Chemother.2000,44:1140-1145
[80]刘芳萍,李昌文,终恒敏.沙门氏菌对哇诺酮类药物耐药性的分子机制[J].中国兽医杂志,2005,41(2)：43
[81]J Rupp M E, Fey P D. Extended spectrum -Lactamase (ESBL) producing Enterobacteriaceae considerations for diagnosis.prevention and drug treatment [J]. Drugs,2003,64(4):353-365
[82]Titus A M, Msagati and Mathew M.Nindi. Determination of β-lactam residues in foodstuffs of animal origin using supported liquid membrane extraction and liquid chromatography-mass spectrometry[J]. Food Chemistry,2007,100: 836-844
[83]Blanco JE, Blanco M, Mora A, et al. Production of toxins (enterotoxins. verotoxins. and necrotoxins) and colicins by Escherichia coli strains isolated from septicemic and healthy chickens:relationship with in vivo pathogenicity[J]. J Clin Microbiol,1997,35:2953-2957
[84]Skyberg JA, Johnson TJ, Johnson JR, et al. Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli isolate enhances its abilities to kill chicken embryos. grow in human urine. and colonize the murine kidney[J]. Infect Immun,2006,74:6287-6292
[85]冯善祥.复方制剂对鸡大肠杆菌病的临床疗效观察[J].中国畜牧兽医,2011,38(2)：236-238
[86]邵泽光,丰西科,高春风.中西药治疗鸡大肠杆菌病的试验[J].中国畜禽种业,2011,1：145-147
[87]朱慧楠,毕可东,刘焕奇,等.氨苄西林混悬液对鸡大肠杆菌病的药效研究[J].安徽农业科学,2009,37(33)：16395-16397
[88]王自然,阮明华.氟苯尼考唬珀酸钠对人工诱发鸡大肠杆菌病的疗效观察[J].中国畜牧兽医,2010,37(4)：212-214.
[89]贾得和.氟苯尼考液对鸡大肠杆菌病的疗效试验[J].上海畜牧兽医通讯,2010,5：48-49
[90]王春华,李慧.氟苯尼考与三甲氧苄啶水溶性粉对试验性鸡大肠杆菌病的疗效研究[J].中国畜牧兽医,2010,37(9)：207-209.
[91]李书宏,王刚,陈庄,等.抗鸡大肠杆菌病复方中药超微粉制剂的研制及药效研究[J].中国畜牧兽医,2010,37(7)：153-157
[92]杜云良,刘彦威,韩博,等.口服头抱拉定对鸡大肠杆菌病的药效研究[J].广东农业科学,2010,3：186-188
[93]龚成珍,严作廷,胡永浩,等.禽健宝对人工感染鸡大肠杆菌肉鸡的预防保护试验[J].湖南农业科学,2010,19：25-129
[94]李树梅,张发明,李应超,等.乌梅酸枣仁提取物对人工感染鸡大肠杆菌病的防治效果[J].中国比较医学杂志,2010,20(6)：49-54
[95]傅艳萍,孙斌,来航线,等.一株拮抗放线菌发酵液对试验性鸡大肠杆菌病的疗效试验[J].中国兽医科学,2009,39(11)：990-993
[96]史同瑞,许腊梅,冯万宇,等.应用微生态制剂防治鸡大肠杆菌病效果[J].当代畜牧,2008,7：13-14.
[97]张敬礼,王双山.中草药对人工感染肉仔鸡大肠杆菌病的防治效果研究[J].安徽农业科学,2008,36(18)：7646-7647
[98]武力,沈祥广,张嘉慧.氟苯尼考水溶性粉对鸡人工感染大肠杆菌的疗效试验[J].福建畜牧兽医,2006,28(4)：17
[99]蔡玉梅,尹逊河,柴同杰,等.人工感染鸡大肠杆菌病的研究[J].中国预防兽医学报,2006,28(3)：356-358
[100]田渊,杨增岐,党如意,等.菌威克对鸡大肠杆菌病的预防和治疗试验[J].中国兽医科技,2004,34(6)：56-58.
[101]周秀红,祁克宗,张丽霞,等.不同接种途径对人工诱发鸡大肠杆菌病的影响[J].安徽农业大学学报,2005,32(4)：463-466
[102]Tivendale KA, Allen JL, Ginns CA, et al. Association of iss and iucA. but not tsh. with plasmid-mediated virulence of avian pathogenic Escherichia coli[J]. Infect Immun,2004,72:6554-6560
[103]Ginns CA, Browning GF, Benham ML, et al. Development and application of an aerosol challenge method for reproduction of avian colibacillosis[J]. Avian Pathol,1998,27:505-511
[104]Gibbs PS,Petermann SR, Wooley RE. Comparison of several challenge models for studies in avian colibacillosis[J]. Avian Dis,2004,48:751-758
[105]Brown PK,Curtiss 3rd R. Unique chromosomal regions associated with virulence of an avian pathogenic Escherichia coli strain[J]. Proc Natl Acad Sci U S A.1996.93:11149-11154
[106]Pourbakhsh SA, Dho-Moulin M, Bree A, et al. Localization of the in vivo expression of P and F1 fimbriae in chickens experimentally inoculated with pathogenic Escherichia coli[J]. Microb Pathog,1997,22:331-341
[107]Kariyawasam S, Wilkie BN, Hunter DB, et al. Systemic and mucosal antibody responses to selected cell surface antigens of avian pathogenic Escherichia coli in experimentally infected chickens[J], Avian Dis,2002,46:668-678
[108]王金莉,李丽.复方头孢噻呋对人工诱发鸡大肠杆菌病的疗效试验[J].中国兽医杂志,2010,4(12)：84-85
[109]王海花,郭宏伟,唐光武.复方盐酸恩诺沙星可溶性粉对实验性鸡大肠杆菌病的疗效试验[J].家畜生态学报,2010,31(1)：93-95
[110]赵英虎,高莉,赵恒寿.硫酸丁胺卡那霉素溶液对鸡大肠杆菌病的临床疗效试验[J].饲料工业,2007,28(8)：48-49
[111]郑雪花,田勇,张煌,等.氟苯尼考水溶性油剂对人工诱发鸡大肠杆菌病的疗效[J].河北北方学院学报(自然科学版),2007,23(6)：39-42
[112]方兰勇,姜中其.氟罗沙星的急性毒性和对鸡实验性大肠杆菌病的药效[J].兽药与饲料添加剂,2001,4：10-11
[113]张红梅.中草药防治畜禽疾病的特点和优势[J].济宁师范专科学校学报,2002,6：27-28
[114]杨淑文.32种中草药抑菌活性的比较研究[J].安徽农业科学,2011,39(3)：1361-1362,1366
[115]王德成,张翠婷.黄芩等六种中草药的体外抑菌试验[J].广东畜牧兽医科技,2010,35(6)：26-28
[116]朱智勇.几种中药制剂的体外抑菌作用研究[J].现代医药卫生,2010,26(13)：2027-2028
[117]李福娟,石学魁,张晓莉,等.苦参、黄连及其配伍的体外抑菌研究[J].牡丹江医学院学报,2010,31(3)：17-19
[118]雷连成,韩文瑜,乔红伟.大肠杆菌耐药性中药抑制剂的初步研究[J].吉林农业大学学报,2003,25(4)：429-433
[119]Weisser J. Elimination of plasmids by enoxacin and ofloacin at near inhibitory concentrations [J]. A ntimicrob Chemother,1986,18(5):575-583
[120]Sonsein SA, Baldwin JN. Loss of the penicillinase plasmid after trement of staphyloccus aureus with sodium dodecyl sulfate[J]. Bacteriol, 1972,109: 262-265
[121]关玛丽,林滢,李泽芬,等.中药娄仁对大肠杆菌(H-(B101)/P-(BR322))质粒的消除作用简报[J].中国人兽共患病杂志,1995,1：25
[122]陈群,王胜春.黄芩和黄连对大肠杆菌R质粒的实验研究[J].广东医学院报,1998,16：1-3
[123]鞠洪涛,韩文瑜,王世若,等.中草药消除大肠埃希氏菌耐药性及耐药质粒的研究[J].中国兽医科技,2000,30(3)：27-29
[124]陈群,王胜春.黄芩与止痢灵对大肠杆菌R质粒消除作用[J].中国微生态学杂志,1998,10(2)：80-82
[125]倪语星,洪秀华.细菌耐药性监测与抗感染治疗[M].北京：人民军医出版社,2002
[126]Barlocco D. Novel boronic acid derivartives as inhibitors of the AmpCp lactamase [J]. Drug Discovery Today,2001,6(17):915
[127]黄通旺,杨灏强.抑制p-内酰胺酶的中草药的筛选研究[J].汕头大学学报(自然科学版),2000,15(2):46-49,54
[128]宋战昀,冯新,韩文瑜,等.金黄色葡萄球菌norA外输泵中药耐药抑制剂的筛选[J].吉林农业大学学报,2007,29(3)：329-333
[129]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报,1995,40(20)：1901-1903
[130]Stermitz. Synergy in a medicinal plant:Antimicrobial action of berberine potentiated by 5-methoxyhydnocarpin.a multidrug pump inhibitor[J]. Applied Biological,2000,97(4):1433-1437
[131]George A M, Levy S B. Amplifiabie resistance to tetracycline chloram-phenicol and her antibiotics in Escherichia coli:involvement of anon plasmid determined efflux of tetracycline[J]. Bacteriol,1983,155(2):531-535
[132]曲宝林,张永强,关现军.中药治疗大肠杆菌效果好[J].当代畜牧,1998(3)：27
[133]杨富业,孙荣华,郑志杰.复方黄连口服液防治鸡大肠杆菌病的研究[J].河南畜牧兽医,1999,20(11)：10-11
[134]胡功政,刘冰宏,班付国,等.加味黄连解毒丸对人工感染大肠杆菌病的治疗效果[J].中国兽医杂志,1998,24(11)：46-67
[135]潘树桥,周晓利,冯喜辉,等.复方中药的制备及对肉用仔鸡大肠杆菌病的防治效果[J].中国兽医科技,2000,30(2)：37-38
[136]范开,张克家,金国星.芩柏龙胆散治疗鸡大肠杆菌并的临床效果观察[J].中西结合,2001,37(6)：30-31
[137]郭世宁,刘宗柱,李金厂,等.中药“禽菌清”防治鸡人工感染大肠杆菌病的研究观察[J].中兽医学杂志,2001,103(2)：11-12
[138]汪德刚,张志远.中药防治鸡大肠杆菌病的实验[J].养禽与禽病防治,2002(9)：14-15
[139]王自然.止泻灵对鸡大肠埃希氏菌耐药和非耐药菌株的治疗实验[J].中国兽医科技,2000,30(9)：35-36
[140]赵俊,傅德桂,沈强兵.中西药治疗大肠杆菌病对产蛋率回升的观察[J].中兽医学杂志,2000,100(3)：21-22
[141]饶茂阳,郁建生.禽痢净口服液的临床效果观察[J].中兽医医药杂志,2001,4：17-18
[142]崔锦鹏,任素芳,颜世敢,等.防治鸡白痢、禽霍乱和大肠杆菌病的中草药方剂筛选及疗效试验[J].山东农业科学,2001,3：34-35
[143]蒋丹,岳静.天南星对人工诱发鸡大肠杆菌病的药效试验[J].鞍山师范学院学报,2003,5(6)：74-76
[144]褚跃成,唐国云.中草药防治鸡病的发展趋向[J].中兽医医药杂志,1998,3：21-22
[145]高菘,刘秀梵.禽大肠杆菌病的研究进展[J].养禽与禽病防治,1999,9：18-20
[146]曾春兰,钟振国.中药抗菌作用的研究进展[J].广西中医学院学报,2006.9(1)：51-53
[147]王永芬,索江华,杨书增,等.鸡大肠杆菌病的流行病学研究进展[J].郑州牧业工程高等专科学校学报,2006,26(3)：18-20
[148]赵坤,赵恒章,王三虎.中药克痢散对鸡大肠杆菌病防治效果研究[J].中国家禽,2003,25(23)：16-18
[149]李明.清瘟止痢散对肉鸡大肠杆菌病的疗效试验[J].广东畜牧兽医科技,2006,31(4)：47-48
[150]沈永恕,吉庆云,马晓海.复方中药“禽痢康”对鸡大肠杆菌病的疗效试验[J].上海畜牧兽医通讯,2009,5：31
[151]Choi JG, Jeong SI, Ku CS, et al. Antibacterial activity of hydroxyalkenyl salicylic acids from sarcotesta of Ginkgo biloba against vancomycin-resistant Enterococcus[J]. Fitoterapia,2009,80:18-20
[152]张深固,蔡海江.新城疫与禽流感病毒等多重感染的西医化疗与中医辨证论治[J].兽医导刊,2010,7：35-37
[153]孔阳,马养民,李彦军,等.车前草提取物抗菌活性的研究[J].中国酿造,2010,10：151-153
[154]王庆银,姚庆强.丹参提取液体外抑菌活性研究[J].食品与药品,2010,12(5)：184-187
[155]马永全,于新,黄雪莲,等.南药五味子提取物的抗菌及抗氧化作用[J].食品与发酵工业,2010,36(6)：45-48
[156]傅文栋.中草药及其有效成分体外抗菌抗病毒研究进展[J].中兽医医药杂志,2006,5：66-67
[157]李树明,张凤鸣,雷燕,等.50味中药对8种畜禽病原菌抑菌对比研究[J].中兽医学杂志,2000,4：5-8
[158]Pandey R, Mishra A. Antibacterial Activities of Crude Extract of Aloe barbadensis to Clinically Isolated Bacterial Pathogens[J]. Appl. Biochem. Biotech.2010,160:1356-1361
[159]Ndhlala AR, Amoo SO, Stafford GI, et al. Antimicrobial. anti-inflammatory and mutagenic investigation of the South African tree aloe (Aloe barberae) [J]. J.Ethnopharmacol,2009,124:404-408
[160]刘志祥,曾超珍,张映辉.穿心莲提取物体外抗菌活性及稳定性的研究[J].北方园艺,2009,1：105-106
[161]Najjaa H, Neffati M, Zouari S, et al.Essential oil composition and antibacterial activity of different extracts of Allium roseum L., a North African endemic species[J]. Comptes Rendus Chimie,2007,10:820-826
[162]郭红珍,姚越红,王秋芬.大蒜抑菌作用的研究[J].安徽农业科学,2007,35(2)：414-415
[163]甄清,李静,李勇,等.锦灯笼宿萼提取物体外抗菌作用研究[J].天然产物研究与开发,2006,18：273-274
[164]宋波,刘頲,吕丽艳,等.苦参、黄芩、乌梅对金黄色葡萄球菌、大肠埃希菌和白假丝酵母菌抗菌活性的研究[J].中国微生态学杂志,2010,22(6)：507-509
[165]孔阳,马养民,李彦军,等.石榴皮粗提物抗菌活性的研究[J].食品科技,2008,9：199-201
[166]刘国生.十五年来中药抗生作用的研究概况[J].中药通报,1958,4(4)：116-120
[167]Yang LX, Liu D, Feng XF, et al. Determination of tlavone for Scutel laria baicalensis from different areas by China[J]. J Chin Mater Med,2002,27: 166-169
[168]刘丹丹,孙君社.大蒜药理作用研究概况[J].中国伤残医学,2007,15(1)：61-63
[169]刘华钢,申庆荣,刘丽敏.中药抗菌研究进展[J].时珍国医医药,2010,21(2)：463-465
[170]Guarda A, Rubilar JF, Miltz J, et al. The antimicrobial activity of microencapsulated thymol and carvacrol[J]. Int J Food Microbiol,2011, in press
[171]Politeo O, Skocibusic M, Maravic A, et al. Chemical Composition and Antimicrobial Activity of the Essential Oil of Endemic Dalmatian Black Pine (Pinus nigra ssp. dalmatica) [J]. Chem Biodivers,2011.8(3):540-547
[172]PK Tarus, PH Coombes, NR Crouch, et al. Benzo[c]phenanthridine alkaloids from stem bark of the Forest Knobwood, Zanthoxylum davyi(Rutaceae)[J]. South African Journal of Botany,2006,72(4):555-558
[173]Molatova Z, Skrivanova E, Macias B, McEwan. N.R et al. Susceptibility of Campylobacter jejuni to organic acids and monoacylglycerols[J]. Folia Microbiol(Praha),2010,55:215-220
[174]Kim KY, Davidson PM, Chung HJ. Antibacterial activity in extracts of Camellia japonica L. petals and its application to a model food system[J]. J Food Prot,2001,64:1255-1260
[175]Kong WJ, Zhao YL, Shan LM, et al. Thermochemical Studies on the Quantity-Antibacterial Effect Relationship of Four Organic Acids from Radix Isatidis on Escherichia coli Growth[J]. Biol. Pharm. Bull.,2008.31:1301-1305
[176]Cunha SC, Ferreira IMPLVO, Fernandes JO, et al. Determination of lactic. acetic. succinic and citric acids in table olives by HPLC/UV. [J]. J. Liq. Chromatogr. R. T.,2001,24:1029-1038
[177]Bozzi A, Perrin C, Austin S, et al. Quality and authenticity of commercial Aloe vera gel powders [J]. Food. Chem.,2007,103:22-30
[178]Moharregh-Khiabani D, Linker RA, Gold R, et al. Fumaric Acid and its Esters:An Emerging Treatment for Multiple Sclerosis[J]. Curr. Neuropharmacol.,2009,7:60-64
[179]Roll A, Reich K, Boer A. Use of fumaric acid esters in psoriasis[J]. Indian journal of dermatology, venereology and leprology,2007,73:133-137
[180]Kreuter A, Gambichler T, Altmeyer P, et al. Treatment of disseminated granuloma annulare with fumaric acid esters[J]. BMC Dermatol.2002,2:5
[181]Comes JE, Beelman RB. Addition of fumaric acid and sodium benzoate as an alternative method to achieve a 5-log reduction of Escherichia coli O157:H7 populations in apple cider[J]. J. Food. Protect.,2002,65:476-483
[182]李建科,马晓萍,蔡玉梅,等.人工诱发鸡大肠杆菌病的接种规律[J].中 国兽医学报,2000,4(20)：372-374
[183]霍清合.大肠杆菌病多发原因及防治[J].家禽科学,2005,3：22-23
[184]郭小清,唐莉苹,聂建超.中药复方颗粒剂救鸡宝对人工诱发鸡大肠杆菌病的疗效观察[J].兽药与饲料添加剂,2004,9(3)：10-11
[185]李世宏,杨国林,巩忠福,等.中草药复方对人工感染鸡大肠杆菌防治试验[J].中兽医医药杂志,2005,4：25-26
[186]胡功政,刘冰宏,班付国,等.中草药对人工感染雏鸡大肠杆菌病的药效研究[J].中兽医学杂志,2001,1：1-2
[187]Ginns CA, Benham ML, Adams LM, et al. Colonization of the respiratory tract by a virulent strain of avianEscherichia coli requires carriage of a conjugative plasmid[J]. Infect Immun,2000,68:1535-1541
[188]Moulin-Schouleur M, Schouler C, Tailliez P, et al. Common virulence factors and genetic relationships between O18:K1:H7 Escherichia coli isolates of human and avian origin[J]. J Clin Microbiol,2006,44:3484-3492
[189]Parreira VR, Gyles CL. A novel pathogenicity island integrated adjacent to the thrW tRNA gene of avian pathogenic Escherichia coli encodes a vacuolating autotransporter toxin[J]. Infect Immun,2003,71:5087-5096
[190]Kariyawasam S, Wilkie BN, Gyles CL. Construction. characterization, and evaluation of the vaccine potential of three genetically defined mutants of avian pathogenic Escherichia coli[J]. Avian Dis,2004,48:287-299
[191]Dozois CM, Daigle F, Curtiss 3rd R. Identification of pathogen-specific and conserved genes expressed in vivo by an avian pathogenic Escherichia coli strain[J]. Proc Natl Acad Sci U S A,2002,100:247-252
[192]Mellata M, Dho-Moulin M, Dozois CM, et al. Role of virulence factors in resistance of avian pathogenic Escherichia coli to serum and in pathogenicity [J]. Infect Immun,2003,71:536-540
[193]Lamarche MG,Dozois CM, Daigle F, et al. Inactivation of the pst system reduces the virulence of an avian pathogenic Escherichia coli O78 strain[J]. Infect Immun,2005,73:4138-4145.
[194]Lymberopoulos MH, Houle S, Daigle F, et al. Characterization of Stg fimbriae from an avian pathogenic Escherichia coli O78:K80 strain and assessment of their contribution to colonization of the chicken respiratory tract[J]. J Bacteriol,2006,188,6449-6459
[195]韦旭斌.中兽医学[M].吉林：吉林科学技术出版社,1997
[196]刘钟杰,许剑琴.中兽医学[M].北京：中国农业出版社,2002,36-115
[197]SM Lutful Kabir. Avian Colibacillosis and Salmonellosis:A Closer Look at Epidemiology. Pathogenesis. Diagnosis. Control and Public Health Concerns[J]. Int. J. Environ. Res. Public Health,2010,7:90
[198]Gyles CL. Antimicrobial resistance in selected bacteria from poultry [J]. Anim Health Res Rev,2008,9(2):149-158
[199]Smith HW, Huggins MB. Effectiveness of phages in treating experimental Escherichia coli diarrhoea in calves, piglets and lambs[J]. J. Gen. Microbiol., 1983,129,2659-2675
[200]Pucci MJ, Bronson JJ, Barrett JF. et al. Antimicrobial evaluation of nocathiacins. a thiazole peptide class of antibiotics[J]. Antimicrob. Agents Chemother.,2004,48:3697-3701
[201]Ana Oliveira, Rui Sereno, Joana Azeredo. In vivo efficiency evaluation of a phage cocktail in controlling severe colibacillosis in confined conditions and experimental poultry houses [J]. Veterinary Microbiology,2010,146:303-308
[202]Lau GL, Sieo CC, Tan WS, et al. Efficacy of a bacteriophage isolated from chickens as a therapeutic agent for colibacillosis in broiler chickens[J]. Poult Sci.,2010,89(12):2589-2596
[203]Oliveira A, Sereno R, Nicolau A. et al. The influence of the mode of administration in the dissemination of three coliphages in chickens[J]. Poult Sci.,2009,88(4):728-733
[204]Johnson RP, Gyles CL, Huff WE.et al. Bacieriophages for prophylaxis and therapy in cattle, poultry and pigs [J]. Anim Health Res Rev,2008,9(2):201 -215
[205]Wang K, Evered MD. Endotoxin stimulates drinking in rats without changing dehydrational signals controlling thirst[J]. Am J Physiol,1993,265(5 Pt 2): R1043-1051
[206]Yirmiya R. Endotoxin produces a depressive like episode in rats[J]. Brain Res, 1996,711:163-168
[207]Calpai G, Squadrito F, Altavilla D, et al. Evidence that nitric oxide modulates drinking behavior[J]. Neuropharmacology,1992,31:761-766
[208]V Raghavendra, JN Agrewala, S K Kulkarni. Role of centrally administered melatonin and inhibitors of COX and NOS in LPS-induced hyperthermia and adipsia[J]. Prostaglandins. Leukotrienes and Essential Fatty Acids,1999, 60(4):249-253
[209]袁东健,陈汝兴.破瘀通脉散对脑缺血-再灌注损伤的影响及机制探讨[J].中国中西医结合急救杂志,1999,10：445
[210]李春盛,桂培春,何新华,等.NO和iNOS在内毒素诱导的大鼠急性肺损伤的作用及大黄对其影响[J].中国急救医学,2000,2：65
[211]孙军,李景峰,姚秀娟,等.山莨菪碱对内毒素休克兔血压及NO生成的影响[J].第四军医大学学报,2000,7：189
[212]Chao WW, Kuo YH, Li WC, et al. The production of nitric oxide and prostaglandin E2 in peritoneal macrophages is inhibited by Andrographis paniculata, Angelica sinensis and Morus alba ethyl acetate fractions[J]. J Ethnopharmacol,2009,122(1):68-75
[213]ChiouWF, Chen CF. Lin JJ. Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide[J]. Br J Pharmaco,2000,129(8):1553-1560
[214]Batkhuu J, HattoriK.Takano F, et al. Supp ression of NO production in activate dmacrophages in vitro and ex vivo by neoandrographolide isolated from A. paniculata [J]. Biol Pharm Bull,2002,25(9):1169-1174
[215]Csilla Becskei. Thomas Riediger, Noemi Hernadfalvy, et al. Inhibitory effects of lipopolysaccharide on hypothalamic nuclei implicated in the control of food intake[J]. Brain. Behavior, and Immunity,2008,22:56-64
[216]Riediger T, Giannini P, Erguven E, Lutz T. Nitric oxide directly inhibits ghrelin-activated neurons of the arcuate nucleus[J]. Brain Res,2006,1125: 37-45
[217]Jansky L, Vybiral S, Pospisilova D, et al. Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever[J].1995, Neuroendocrinology,62:55-61
[218]Plata-Salaman CR, Oomura Y, Kai Y. Tumor necrosis factor and interleukin-1b:suppression of food intake by direct action in the central nervous system[J]. Brain Res,1988,448:106-114
[219]Basa NR, Wang L, Arteaga JR, et al. Bacterial lipopolysaccharide shifts fasted plasma ghrelin to postprandial levels in rats[J]. Neurosci. Lett.,2003,343: 25-28
[220]王春光,张铁,蒋桂娥.鸡大肠杆菌病血清NO. TNF-α水平检测及临床意义[J].黑龙江畜牧兽医,2010,7：86-87
[221]张涛.穿心莲的研究最新进展[J].中药材.2000.23(6)：366-368
[222]Coon JT, Ernst E. Andrographis paniculata in the treatment of up-per respiratory tract in fections:asystematic review of safety and efficacy[J]. Planta Med,2004,70(4):293-298
[223]路景涛,陈敏珠.复方黄茂提取物对细菌脂多糖诱导大鼠腹腔巨噬细胞分泌TNF-α,NO及IL-1的影响[J].安徽医药,2006,10(5)：330-331
[224]高斌,高洪,严玉霖.内毒素对兔红细胞膜磷脂含量的影响及阳离子A对其的拮抗效应[J].中国兽医学报,2006,26(4)：397-401
[225]Frede S, Fandrey J, Pagel H, et al. Erythropoietin gene expression is suppressed after lipopolysaccharide or interleukin-1 beta injections in rats[J]. Am J Physiol,1997.273:R1067-1071
[226]Tillema MS, Lorenz KL. Weiss MG, et al. Sublethal endotoxemia promotes pulmonary cytokine-induced neutrophil chemoattractant expression and neutrophil recruitment but not overt lung injury in neonatal rats[J]. Biol Neonate,2000,78:308-314
[227]Goyette RE, Key NS, Ely EW. Hematologic changes in sepsis and their therapeutic implications [J]. Semin Respir Crit Care Med,2004,25:645-659
[228]Antonella Di Mario, Mariagrazia Garzia, Fiammetta Leone. Immature platelet fraction (IPF) in hospitalized patients with neutrophilia and suspected bacterial infection[J]. Journal of Infection,2009,59:201-206
[229]Chang CF, PB Hamilton. The thrombocyte as the primary circulating phagocyte in chickens [J]. J. Reticuloendothel.Soc.,1979,25:585-590
[230]Meseguer J, M A Ngeles Estban, AR Guez. Are thrombocytes and platelets true phagocytes [J]. Microsc. Res. Tech.,2002,57:491-497
[231]George JN. Platelets [J]. Lancet,2000,355:1531-1539
[232]Jay Menaker, Ian Bebvon K Martin, Jon Mark Hirshon, et al. Marked elevation of cerebrospinal fluid white blood cell count:An unusual case of Streptococcus pneumoniae meningitis. differential diagnosis. and a brief review of current epidemiology and treatment recommendations [J]. Journal of Emergency Medicine,2005,29(1):37-41
[233]Klinger MH. Platelets and inflammation[J]. Anat. Embryol. (Berl.),1997, 196:1-11
[234]林曦.家畜病理学[M].北京：中国农业出版社,1997：8-91
[235]林曦.家畜病理学[M].北京：中国农业出版社,1997：241-242
[236]任玉红,黄素珍.肉仔鸡急性大肠杆菌病病理学观察[J].肉品卫生,1997,10：1-3
[237]蒋建新.细菌内毒素基础与临床[M].北京：人民军医出版社,2004：8
[238]Dinarello CA. Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism [J]. Int J Tissue React,1992, 4:65-75
[239]Murch SH. Local and Systemic Effects of Macrophage Cytokines in Intestinal Inflammation[J]. Nutrition,1998,14:780-783
[240]Dai Y. Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway[J]. Journal of Natural Medicines,2009,63:421-429
[241]Lynn WA, Cohen J. Adjunctive therapy for septic shock:a review of experimental approaches[J]. Clinical Infectious Diseases,1995,20:143-158
[242]Ozmen L, Pericin M, Hakimi J, et al. Interleukin 12. interferon. and tumor necrosis factor are the key cytokines of the generalized Schwartzmann reaction[J]. Journal of Experimental Medicine,1994,180:907-915
[243]Fisher CJJr, Yan SB. Protein C levels as a prognostic indicator of outcome in sepsis and related diseases[J]. Critical Care Medicine,2000.28:S49-56
[244]Mesters RM. Helterbrand J, Utterback BG, et al. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications[J]. Critical Care Medicine,2000,28:2209-2216
[245]Esmon CT. The Protein C Pathway[J]. Chest,2003,124:26S-32S
[246]Regan LM, Stearns-Kurosawa DJ, Kurosawa S, et al. The endothelial cell protein C receptor:inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors [J]. Journal of Biological Chemistry,1996,271:17499-17503
[247]Griffin JH, Hartman DL. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications[J]. Critical Care Medicine.2000,28:2209-2216
[248]裴忠绳.浅谈鸡病的辫证施治[J].中兽医医药杂志,1996,2：19-20
[249]Libby P. Simon DI. Inflammation and Thrombosis:The Clot Thickens[J]. Circulation.2001,103:1718-1720
[250]Sheeja K, Shihab PK, Kuttan G. Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata Nees[J]. Immunopharmacology and Immunotoxicology,2006,28:129-140
[251]Parichatikanond W, Suthisisang C. Dhepakson P, et al.. Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression[J]. International Immunopharmacology,2010,10(11):1361-1373
[252]Liu J, Wang ZT, Ge BX. Andrograpanin. isolated from Andrographis paniculata. exhibits anti-inflammatory property in lipopolysaccharide-induced macrophage cells through down-regulating the p38 MAPKs signaling pathways[J]. International Immunopharmacology,2008,8:951-958
[253]Gao XH, Xu XX, Pan R, et al. Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway[J]. Journal of Natural Medicines,2009,63:421-429
[254]Gao XH, Xu XX, Pan R et al. Qi-Shao-Shuang-Gan. a Combination of Astragalus membranaceus Saponins with Paeonia lactiflora Glycosides.Ameliorates Polymicrobial Sepsis Induced by Cecal Ligation and Puncture in Mice [J]. Inflammation,2011:4(1):10-21
[255]Ewers C, Janssen T, Wieler LH. Avian pathogenic Escherichia coli (APEC)[J]. Berl Munch Tierarztl Wochenschr,2003,116:381-395
[256]Dho-Moulin M, Fairbrother JM. Avian pathogenic Escherichia coli (APEC) [J]. Vet Res,1999,30:299-316
[257]Dho-Moulin M, van den Bosch JF, Girardeau JP, et al. Surface antigens from Escherichia coli 02 and 078 strains of avian origin[J]. Infect. Immun.,1990, 58:740-745
[258]Dozois CM, Fairbrother JM, Harel J, et al. Pap-and pil-related DNA sequences and other virulence determinants associated with Escherichia coli isolated from septicemic chickens and turkeys[J]. Infect. Immun.,1992,60,2648-2656
[259]van den Bosch JF, Hendriks JH, Gladigau I, et al. Identification of F11 fimbriae on chicken Escherichia coli strains[J]. Infect. Immun.,1993,61: 800-806
[260]Ellis MG, Arp LH, Lamont SJ. Serum resistance and virulence of Escherichia coli isolated from turkeys[J]. Am. J. Vet. Res.,1988,49:2034-2037
[261]Pfaff-McDonough SJ, Home SM, Giddings CW, et al. Complement resistance-related traits among Escherichia coli isolates from apparently healthy birds and birds with colibacillosis[J]. Avian Dis,2000,44:23-33
[262]Chaffer M, Heller ED, Schwartsburd B. Relationship between resistance to complement, virulence and outer membrane protein patterns in pathogenic Escherichia coli O2 isolates [J]. Vet. Microbiol.,1999,64:323-332
[263]Emery DA, Nagaraja KV, Shaw DP. et al. Virulence factors of Escherichia coli associated with colisepticemia in chickens and turkeys[J]. Avian Dis, 1992,36:504-511
[264]Blanco JE, Blanco M, Mora A, et al. Production of toxins (enterotoxins. verotoxins. and necrotoxins) and colicins by Escherichia coli strains isolated from septicemic and healthy chickens:relationship with in vivo pathogenicity[J]. J. Clin. Microbiol.,1997,35:2953-2957
[265]Parreira VR, Yano T. Cytotoxin produced by Escherichia coli isolated from chickens with swollen head syndrome (SHS) [J]. Vet. Microbiol.,1998,62: 111-119
[266]VL Waters, JH Crosa. Colicin V Virulence Plasmids[J]. Microbiological Reviews,1991,55 (3):437-450
[267]Van Alstine WG, Arp LH. Effects of Bordetella avium infection on the pulm onary clearance of Escherichia coli in tur keys[J]. Am J Vet Res,1987,48: 922-926
[268]Maina IN. Scanning electro n microscope study of the spatia 1 organization of the air and blood conductingcomponents of the avian lung (Gallus Gallus variant domesticus) [J]. Anat Rec,1988.222:145-153
[269]Jones AW, Radn. The development of the chick tert iary bronchus. I. General development and the mode of produ ction of the osmio philic inclusion body[J]. J Anat,1972,113:303-324
[270]Maina IN, King AS. The thickness of the avian bloodgas barrier:qual itati ve and quantitat ive obser vations[J]. J Anat,1982,134:553-562
[271]Qiang Shen, Robert R Rigor, Christopher D. Pivetti. Myosin light chain kinase in microvascular endothelial barrier function[J]. Cardiovascular Research, 2010,87:272-280
[272]Yuan SY. Protein kinase signaling in the modulation of microvascular permeability[J]. Vascul Pharmacol,2002,39:213-223
[273]F Moccia, S Baruffi, S Spaggiari, et al. P2Y1 and P2Y2 Receptor-Operated Ca21 Signals in Primary Cultures of Cardiac Microvascular Endothelial Cells[J]. Microvascular Research,2001,61,240-252
[274]张涛,滕可导,田启超,等.乳鼠心肌膜微血管内皮细胞的体外培养[J].解剖学报,2008,39(1)：121-123
[275]司徒镇强,吴军正.细胞培养[M].西安：世界图书出版公司,2004：81-84
[276]RS McCuskey, Renate Urbaschek, Bernhard Urbaschek. The microcirculation during endotoxemia[J]. Cardiovascula Rresearch,1996,32:752-763
[277]Andrea Nencioni, Stephen Trzeciak, Nathan I Shapiro. The microcirculation as a diagnostic and therapeutic target in sepsis[J]. Intern Emerg Med,2009, 4:413-418
[278]Lehr HA, Bittinger F, Kirkpatrick CJ. Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy [J]. J Pathol,2000,190:373-386
[279]Vallet B. Endothelial cell dysfunction and abnormal tissue perfusion[J]. Crit Care Med,2002,30(S5):229-234
[280]WO Twal, RM Leach. Isolation And Characterization of Micro Vascular Endothelial Cells From Chicken Fat Pads[J]. In Vitro Cell. Dev Biol. Animal, 1996,32:403-408
[281]David Waddington, AJ Springbett, DW Burt A Chromosome-Based Model for Estimating the Number of Conserved Segments Between Pairs of Species From Comparative Genetic Maps [J]. Genetics,2000,154 (1):323-332
[282]RPMA Crooijmans, RJM Dijkhof, Tineke Veenendaal. The Gene Orders on Human Chromosome 15 and Chicken Chromosome 10 Reveal Multiple Inter-and Intrachromosomal Rearrangements[J]. Mol. Biol. Evol.,2001,18(11): 2102-2109
[283]Adler HE, DaMassa AJ. Toxicity of endotoxin to chicks[J]. Avian Dis,1979, 23(1):174-178
[284]YB Shen, XS Piao, SW Kim, et al. The effects of berberine on the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide in broiler chickens[J]. Poult Sci.2010,89(1):13-19
[285]de Boever S, Neirinckx EA, Meyer E, et al. Pharmacodynamics of tepoxalin. sodium-salicylate and ketoprofen in an intravenous lipopolysaccharide inflammation model in broiler chickens[J]. J. vet. Pharmacol. Therap.,2010. 33:564-572
[286]De Boever S, Croubels S, Meyer E. et al. Characterization of an intravenous lipopolysaccharide inflammation model in broiler chickens[J]. Avian Pathology,2009,38:403-411
[287]RS McCuskey, Renate Urbaschek, Bernhard Urbaschek. The microcirculation during endotoxemia[J]. Cardiovascula Rresearch,1996,32:752-763
[288]Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease[J]. N Engl J Med,2000,342:1792-1801
[289]Aso Y. Fibrinolysis and cardiovascular disease in type 2 diabetes:roles of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor[J]. Future Lipidology,2006,1:429-440
[290]Fay WP, Garg N, Sunkar M. Vascular functions of the plasminogen activation system[J]. Arterioscler Thromb VascBiol,2007.27:1231-1237
[291]Sprengers ED, Kluft C. Plasminogen activator inhibitors[J]. Blood.1987. 69:381-387
[292]Zorio E, Gilabert-Estelles J, Espana F, et al. Fibrinolysis:The key to new pathogenetic mechanisms[J]. Curr Med Chem,2008,5:923-929
[293]Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: Studies of PAI-1[J]. Arterioscler Thromb Vasc Biol,1998,18:1-6
[294]Weisberg AD, Albornoz F, Griffin JP, et al. Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling[J]. Arterioscler Thromb VascBiol,2005, 25:365-371
[295]Aso Y. Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis[J]. Front Biosci,2007,12:2957-2966
[296]van Hinsbergh VW, Kooistra T, van den Berg EA, et al. Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo[J]. Blood,1988,72:1467-1473
[297]Yunzi Chen, Juan Kong, Tao Sun, et al.1.25-Dihydroxyvitamin D3 suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-KB activation[J]. Archives of Biochemistry and Biophysics,2011,507 (2):241-247
[298]Liu X, Peng YM, Liu FY, et al. Effect of indomethacin on fibronectin and plasminogen activator inhibitor-1 in cultured human peritoneal mesothelial cells[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban,2005,30(5):590-592, 603
[299]Dong J, Fujii S, Imagawa S, et al. IL-1 and IL-6 induce hepatocyte plasminogen activator inhibitor-1 expression through independent signaling pathways converging on C/EBP delta[J]. Am J Physiol Cell Physiol,2007, 292:209-215
[300]阮秋蓉,宋建新,邓仲端.山莨菪碱抗血栓形成的机制研究[J].中华病理学杂志,2000,29(3)：212-215
[301]阮秋蓉,宋建新,邓仲端.川芎嗪抗血栓形成的机制研究[J].中国动脉硬化杂志,1998,6(4)：297-300
[302]周喆.复方丹参方活性单体对TNF-α损伤人血管内皮细胞的保护作用[D].北京：中国人民解放军军事医学科学院,2005
[303]王宗仁,郑瑾,马爱玲,等.中药芪丹通脉片对动脉粥样硬化大鼠主动脉内皮细胞及PAI-1表达影响[J].第四军医大学学报,2004,25(14)：1290-1293
[304]郑培永,安德明,季光.不同治则中药复方对胆汁淤积性肝纤维化大鼠PAI-1影响的研究[J].中西医结合肝病杂志,2007,17(5)：284-287
[305]刘春生,陈和平,韩淑莲,等.利肾血冲剂对慢性肾炎血瘀型患者血清中t-PA、PAI-1的影响及临床意义[J].中医研究,2008,21(4)：28-30
[306]杨长春,马增春.黄芪、当归对血管内皮细胞纤溶酶原激活物抑制剂-1的影响[J].第三军医大学学报,2010,32(11)：1149-1151
[307]何晓峰,刘蔚,刘晓城,赵晓琴等.黄芪对左肾静脉狭窄大鼠肾组织TGF-β1和PAI-1表达的影响[J].中国组织化学与细胞化学杂志,2008,17(3)：247-251
[308]MackmanN. The many faces of tissue factor[J].J ThrombHaemost.2009. 7(S1):136-139
[309]Kasthuri RS, Taubman MB, Mackman NJ. Role of tissue factor in cancer[J]. Clin Oncol,2009,27(29):4834-4838
[310]Breitenstein A, Tanner FC, LTF Circ J. Tissue factor and cardiovascular disease:quo vadis[J].2010,74(1):3-12
[311]Gross PL, Vaezzadeh N. Tissue factor microparticles and haemophilia[J]. Thromb Res,2010,125 (SI) : 67-69
[312]Pixley RA, De La Cadena R, Page JD, et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal antifactor XII antibody to block contact activation in baboons[J]. J Clin Invest,1993,91:61-68
[313]Shimura M, Wada H, Wakita Y, et al. Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation[J]. Am J Hematol,1996,52:165-170
[314]Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis[J]. Am J Pathol,1989,134:1087-1097
[315]Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis[J]. Arterioscler Thromb Vasc Biol, 2007,27:1687-1693
[316]Pawlinski R, Tencati M, Holscher T, et al. Role of cardiac myocyte tissue factor in heart hemostasis[J]. J Thromb Haemost,2007,5:1693-1700
[317]de Ward V, Hansen HR, Spronk HH, et al. Differential expression of tissue factor mRNA and protein expression in murine sepsis. The role of the granulocyte revisited[J]. Thromb Haemost,2006,95:348-353
[318]Erlich J, Fearns C, Mathison J, et al. Lipopolysaccharide induction of tissue factor expression in rabbits [J]. Infect Immun,1999,67:2540-2546
[319]Mizumura K, Gon Y, Kumasawa F, et al. Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates lipopolysaccharide-induced tissue factor expression in pulmonary microvasculature[J]. Int Immunopharmacol, 2010,10(9):1062-1067
[320]Kim I, Oh JL, Ryu YS, et al. Angiopoietin-1 negatively regulates expression and activity of tissue factor in endothelial cells[J]. FASEB J,2002,16(1): 126-128
[321]文志斌,尚改萍,何晓凡,等.补阳还五汤对凝血酶诱导血管内皮细胞释放No、vWF、TFPI及表达组织因子的影响[J],湖南医科大学学报,2002,27(4)：315-319
[322]尚改萍,文志斌,李俊成,等.补阳还五汤对TNF-α诱导血管内皮细胞释放vWF及表达组织因子的影响[J].湖南医科大学学报,2000,25(2)：129-131
[323]何晓凡,文志斌,贺石林.四物汤对脂多糖诱导乳鼠星形胶质细胞表达组织因子的影响[J].血栓与止血学,2004,10(3)：104-106
[324]成春英,文志斌.何晓凡,等.灵芝合剂对乳鼠星形胶质细胞组织因子表达的影响[J].中国比较医学杂志,2006,16(5)：263-266
[325]张玉珠,张艳,于睿,等.益气活血复方对动脉粥样硬化家兔纤溶系统及TF的影响[J].中华中医药学刊,2009,27(11)：2333-2337
[326]汪自龙,李东野,夏勇,等.葛根素对急性冠脉综合征患者体外单核源巨噬细胞MMP-9及TF的影响[J].江苏中医药,2008,40(5)：87-88
[327]谢薇,夏凌辉,方峻,等.人参皂苷Rb1对白消安诱导人脐静脉内皮细胞表达PAI-I、TF和TGF-β1的影响[J].中国病理生理杂志,2008,24(9)：1856-1858
[328]熊石龙,文志斌,何晓凡,等.川芎嗪抑制TNF-α诱导人脐静脉血管内皮细胞组织因子表达的机制研究[J].广东医学,2008,29(4)：545-548
[329]Holp EW, Aklnnedov A, Luscher TF, et al. Berberine, a natural lipid-lowering drug, exerts prothrmnbotic effects on vascular cells[J], J Mol Cell Cardial, 2009,46(2):234-240
[330]Kaur G, Roberti M, Ralul F, et al. Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol[J]. Thromb Res,2007,119(2):247-256
[331]Li YD, Ye BQ, Zheng SX, et al. NF-kappaB transcription factor p50 critically regulates tissue factor in deep vein thrombosis [J]. J Biol Chem,2009,284(7): 4473-4483
[332]孙慧燕,孟祥艳,罗玉玉,等.Kruppel样锌指转录因子在内皮细胞中的生物学作用[J].武警医学院学报,2009,18(2)：165-168
[333]Botella LM, Sanchez-Eisner T, Sanz-Rodriguez F, et al, Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Spl and KLF6:their potential role in the response to vascular injury[J]. Blood,2002,100:4001-4010
[334]Kojima S, Hayashi S, Shimokado K, et al. Transcriptional activation of urokinase by the Kruppel-like factor Zf9/COPEB activates latent TGF-betal in vascular endothelial cells[J]. Blood.2000.95:1309-1316
[335]Kuo CT, Veselits ML. Barton KP, et al. The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis[J], Genes Dev,1997,11:2996-3006
[336]Yet SF, McA Nulty MM, Folta SC, et al. Human EZF. a Kruppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains[J]. J Biol Chem,1998,273: 1026-1031
[337]SenBanerjee S, Lin Z, Atkins GB, et al. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation[J]. J Exp Med,2004,199: 1305-1315
[338]Zhiyong Lin, Ajay Kumar, Sucharita SenBanerjee, et al. Kruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function[J]. Circ. Res.,2005, 96:48-57
[339]Dekker RJ, van Soest S, Fontijn RD, et al. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2)[J]. Blood,2002,100:1689-1698
[340]Kumar A, Lin Z, SenBanerjee S, et al. Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of MEF2 by NF-kappaB and histone deacetylases[J]. Mol Cell Biol,2005,25:5893-5903
[341]陈理国,张聪,郑仲谨,等.全身炎症反应综合证发生的分子机制研究进展[J].西南国防医药,2003,13(5)：566-569
[342]窦肇华,张远强,郭顺根.免疫细胞学与疾病[M].北京：中国医药科技出版社,2004,9：771-785
[343]张涛,黄会岭,胡格,等.小檗碱、绿原酸和黄芩苷对LPS损伤大鼠肠黏膜微血管内皮细胞表达ICAM-1的影响[J].畜牧兽医学报,2008,39(4)：499-502
[344]林红,胡格,伊鹏霏,等.黄芩苷、连翘酯苷对肺微血管内皮细胞分泌IFN-a、IFN-γ的影响[J].中国畜牧兽医,2009,36(6)：30-34
[345]解慧梅,胡格,索占伟,等.人参皂甙Rbl和黄芪多糖对微血管内皮细胞分泌NO、IL-6和TNF-α的影响[J].畜牧兽医,2006,37(9)：903-907
[346]Bochud PY, Calandra T. Pathogenesis of sepsis:new concepts and implications for future treatment [J]. Bmj,2003,326:262-266
[347]Zentella A.Manogue K, Cerami A. The role of cachectin/TNF and other cytokines in sepsis[J]. Prog Clin Biol Res,1991,367:9-24
[348]Nathan C. Points of control in inflammation[J]. Nature,2002,420:846-852
[349]Ronald JA, Ionescu CV, Rogers KA, et al. Differential regulation of transendothelial migration of THP-1 cells by ICAM-1/LFA-1 and VCAM-1/VLA-4[J]. J Leukoc Biol,2001,70:601-609
[350]Yang, Domingos NCK, M WS. Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium[J]. The Journal of Biological Chemistry,2002,277:46364-46373
[351]Madge LA, Pober JS. TNF signaling in vascular endothelial cells[J]. Exp Mol Pathol,2001,70:317-325
[352]Tracey KJ, Cerami A. Tumor necrosis factor:An updated review of its biology[J]. Crit Care Med.1993,21:S415-S422
[353]Al-Aly Z. Arterial calcification:a tumor necrosis factor-alpha mediated vascular Wnt-opathy[J], Transl Res.2008,151:233-239
[354]Strieter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-[alpha] in disease states and inflammation[J]. Crit Care Med,1993,21:S447-S463
[355]Mammen EF. Perspectives for the future [J]. Intensive Care Med,1993,19: S29-S34
[356]Pennica D, Nedwin G E, Hayflick J S, et al. Human tumour necrosis factor: precursor structure. expression and homology to lymphotoxin [J]. Nature, 1984,312(5996):724-729
[357]Vilcek J, Lee TH. Tumor necrosis factor[J]. J Biol Chem,1991,266:7313-7316
[358]Schmid EF, Binder K, Grell M, et al. Both tumor necrosis factor receptors. TNFR60 and TNFR80. are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor [alpha] [J]. Blood,1995,86: 1836-1841
[359]Miwa Morita. Shozo Yano, Toru Yamaguchi, et al. Phenylacetic Acid Stimulates Reactive Oxygen Species Generation and Tumor Necrosis Factor-a Secretion in Vascular Endothelial Cells[J]. Therapeutic Apheresis and Dialysis,2011,15(2):147-150
[360]Cendan JC, Moldawer LL, Souba WW, et al. Endotoxin-induced nitric oxide production in pulmonary artery endothelial cells is regulated by cytokines[J]. Arch Surg,1994,129:1296-1300
[361]Yiyi Hu, Xi Chen, Hong Lin, et al. Study on the antiendotoxin action of Pulsatillae Decoction using an Affymetrix rat genome array[J]. Cellular Immunology,2009,257,32-37
[362]Cendan JC, Moldawer LL, Souba WW, et al. Endotoxin-induced nitric oxide production in pulmonary artery endothelial cells is regulated by cytokines[J]. Arch Surg,1994,129:1296-1300
[363]Schmid EF, Binder K, Grell M, et al. Both tumor necrosis factor receptors. TNFR60 and TNFR80. are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor [alpha] [J]. Blood,1995,86: 1836-1841
[364]Tadaatsu Imaizumi, Hiroyuki Itaya, Kazumi Fujita, et al. Expression of Tumor Necrosis Factor-a in Cultured Human Endothelial Cells Stimulated With Lipopolysaccharide or Interleukin-1α[J]. Arterioscler Thromb Vasc Biol, 2000,20(2):410-415
[365]张云香,王家富.血管内皮细胞损伤与肿瘤坏死因子α的因果效应[J].中国临床康复,2005,9(27)：123-125
[366]Fabry Z, Waldschmidt MM, Hendrickson D, et al. Adhesion molecules on murine brain microvascular endothelial cells:Expression and regulation of ICAM-1 and Lgp 55[J]. J. Neuroimmunol.,1992,36:1-11
[367]Wong D, Dorovini-Zis K. Up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression on primary cultures of human brain microvessel endothelial cells by cytokine and lipopolysaccharide [J]. J. Neuroimmunol., 1992,39:11-22
[368]Luo X, Miao CH, Ge BX, et al. Effects of isoflurane, sevoflurane and desflurane on expression of ICAM-1 and VCAM-1 in LPS-induced rat lung microvascular endothelial cells[J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2010,39(5):464-469
[369]Fichtner F, Koslowski R, Augstein A, et al. Bleomycin induces IL-8 and ICAM-1 expression in microvascular pulmonary endothelial cells[J]. Exp Toxicol Pathol,2004,55(6):497-503
[370]Sawa Y, Ueki T, Hata M, et al. LPS-induced IL-6. IL-8. VCAM-1. and ICAM-1 expression in human lymphatic endothelium[J]. J Histochem Cytochem,2008,56(2):97-109
[371]Pressner K T, May A E, Wohn K D, et al. Molecular adhesion receptors and proteolytic cascade in vascular remodeling [J]. Thromb Hemost,1997,78(1):88
[372]Diacovo TG, Roth SJ, Buccola JM, et al. Neutrophil rolling, arrest, and transmigration across activated. surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD 18[J]. Blood.1996,88:146-157
[373]Diamond MS, Staunton DE, de Fougerolles AR, et al. ICAM-1 (CD54):A counter-receptor for Mac-1 (CDllb/CD18)et al. J Cell Biol,1990,111:3129-3139
[374]Dianzani C, Brucato L, Gallicchio M, et al. Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial cells by inhibiting ICAM-1 and VCAM-1 expression[J]. Br J Pharmacol,2008,153(6):1153-1161
[375]曲晓梅,金钟太,尚艳华,等.甘草水煎液抗炎作用的实验研究[J].实用药物与临床,2005,8(5)：14-16
[376]Chang YL, Chen CL, Kuo CL, et al. Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-kappaB pathways in TNF-alpha-activated endothelial cells[J]. Acta Pharmacol Sin,2010,31(5):546-553
[377]Xiping Z,Dijiong W, Jianfeng L, et al. Effects of Salvia miltiorrhizae on ICAM-1. TLR4. NF-kappaB and Bax proteins expression in multiple organs of rats with severe acute pancreatitis or obstructive jaundice[J]. Inflammation, 2009.32(4):218-332
[378]Philpott DJ, Yamaoka S. Invasive Shigella fexneri actives NF-KB through a lipopolysaccharide-dependent innate intracellular response and leads toll-8 expression in epithelial cells [J]. Immunol,2000,165:903-914
[379]Sun Z, Andersson R. NF-kB activation and inhibition:a review[J]. Shock, 2002,18(2):99-106
[380]Muller JM, Loms Ziegler-Heitbrock HW, Baeuerle PA. Nuclear factor kappa B a mediator of lipopolysaccharide effects[J]. Immunobiology,1993,187: 233-256
[381]Llui's E, Julia IE, Alex RM, et al. I-KB and p65 regulate the cytoplasmic shuttling of nuclear corepressors:Cross-talk between notch and NF-KB pathways [J]. Molecular Biology of the Cells,2003,14:491-494
[382]Zhang B, Shouping G, Chang C, et al. A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-KB Pathway[J]. Am J Respir Crit Care Med,2009,179(8):657-665
[383]Wang YJ, Wang JT, Fan QX, et al. Andrographolide inhibits NF-κB activation and attenuates neointimal hyperplasia in arterial restenosis[J]. Cell Research, 2007,17:933-941
[384]Chen YH, Lin SJ, Ku HH, et al. Salvianolic Acid B Attenuates VCAM-1 and ICAM-1 Expression in TNF-a-Treated Human Aortic Endothelial Cells[J]. Journal of Cellular Biochemistry,2001,82:512-521
[385]Zhang WJ, Hufnagl P, Binder BR, et al. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression[J]. Thromb Haemost,2003,90(5):904-914
[2]Otaki Y.Poultry disease control programme in Japan[J].Asian Livestock,1995, 20:65-67
[3]史喜菊,郑明学,冯梁.鸡大肠杆菌病最新研究进展[J].畜禽业,2000,174(8)：14-16
[4]陆承平主编.兽医微生物学(第三版)[M].北京：中国农业出版社,2001：215-223
[5]韩文瑜,何昭阳,刘玉斌主编.病原细菌检验技术[M].吉林科学技术出版社,1992：270-271
[6]Yaguchi K, Ogitani T, Osawa R, et al. Virulence factors of avian pathogenic Escherichia coli strains isolated from chickens with colisepticemia in Japan[J]. Avian Dis,2007,51(3):656-62
[7]Chart H, Smith HR, La Ragione, et al. An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5α and EQ1 [J]. J. Appl. Microbiol,2000,89:1048-1058
[8]恽时锋,潘震寰,郑明球.鸡大肠杆菌病研究进展[J].畜牧与兽医,1998,30(6)：277-280
[9]蔡宝祥.家畜传染病学(第四版)[M]..北京：中国农业出版社,2001
[10]夏业才,潘松年.禽大肠杆菌病的研究鸡致病性大肠杆菌的血清型鉴定[J].中国兽药杂志,1991,25(4)：1-2
[11]林维庆.鸡大肠杆菌病[J].华南农业大学学报,1991,12(3)：7-13
[12]王晶钰,张国祥,王英珍,等.陕西省鸡致病性大肠杆菌的分离及血清型鉴定和药敏试验[J].中国兽医科技,1996,26(3)：15-17
[13]陈绍熙,梁国芳,郭强,等.鸡大肠杆菌病病原分离鉴定和多价蜂胶灭活苗的研制[J].中国畜禽传染病,1997,2：22-25
[14]周继宏,朱国强,庄国宏,等.鸡致病性大肠杆菌的分离与鉴定[J].中匡 畜禽传染病,1997,19(6)：27-28
[15]邵华斌,杨峻,黎秋花,等.湖北省鸡大肠杆菌病流行情况调查及病原分离鉴定[J].中国兽医科技,1998,28(9)：14-15
[16]高轩,李潭清.河北省禽病原性大肠杆菌的血清型鉴定[J].河北农业大学学报,1998,21(1)：56-59
[17]李玉文,李惠兰,齐景文,等.辽宁省禽大肠埃希氏菌血清型的调查及其致病性试验[J].中国兽医科学,2006,36(8)：630-633
[18]丁伯良,鄢明华,王英珍,等.天津地区鸡致病性大肠杆菌血清型分布及其优势血清型的外膜蛋白型研究[J].动物医学研究进展,2003.24(2)：94-96
[19]刘远飞,曹翠萍,宁海强,等.山东省鸡大肠杆菌血清型分布及耐药性分析[J].家畜生态学报,2008,29(1)：88-90
[20]魏麟,黎晓英,刘胜贵,等.湖南西部地区鸡大肠杆菌血清型分布及耐药性分析[J].安徽农业科学,2009,37(28)：13615-13617
[21]戴鼎震,恽时锋.鸡源性大肠杆菌菌毛研究进展[J].湖北农学院学报.1999.19(4)：371
[22]Weiser JN, Gotschlich EC. Outer membrane protein A (OmpA) contributes to serum resistance and pathogenicity of Escherichia coli K-1 [J]. Infect immune. 1991,59(7):2252-2258
[23]NolanLK, Wooley R E, Cooper PK, et al. Transposon mutagenesis used to study the role of complement resistnace in the vimlence of an vaian Eseherichia coli isolate[J]. Avian Disease,1992,36:398-400
[24]LeeMn, Wooley R E, Brown J, et al. Comparison of aquantitative microtiter method aquantitative automated method and the plate-count method for detemrining mierobial complement resistnaee[J]. Avina Diseasa,1991,35: 892
[25]陈红玲,何芳,朱兴全,等.鸡大肠杆菌病及其防治[J].广东畜牧兽医科技,2003,28(3)：30-33
[26]彭德旺,葛兆宏,王涛,等.养鸡技术讲座[J].甘肃畜牧兽医.1995,124(5):32-35
[27]陈静,王贵升,田夫林,等.山东省鸡大肠杆菌和沙门氏菌的发病趋势和耐药性变化分析[J].中国兽医杂志,2006,40(2)：19-22
[28]钟映梅,刘宏雨,孙刚,等.应用试剂条对大肠杆菌病的诊断与防制[M].第15届世界禽病大会论文集,2007：165
[29]于金玲,刘孝刚,张书杰,等。产蛋鸡传染性喉气管炎与大肠杆菌病混合感染的诊治[J].辽宁畜牧兽医,2003,5：18
[30]甘孟候.中国禽病学[M].北京：中国农业出版社,1999,168-174
[31]Deb JR et al. Lab.Trials with inactivated vaccines against E.coli (O78:K80) infection in fowls [J]. Res Vet Sci,1976,20:131-138
[32]Panigrahy B. Immunogenic potency of an oil-emulsified E.coli bacterin [J]. Avian Diseases,1983,27(2):475-481
[33]Morley A J. Swollen-head syndrome in broiler chickens [J]. Avian Diseases, 1984,28(1):238-243
[34]梁国芳,陈绍熙,郭强,等.鸡大肠杆菌多价蜂胶灭活苗的研制[J].中国畜禽传染病,1997,19(6)：37-39
[35]杨峻,邵华斌,刘泽文,等.鸡大肠杆菌病多价蜂胶灭活疫苗的研究[J].湖北畜牧兽医,1999,3：9-13
[36]张安国,沈华,马文芝,等.鸡大肠埃希氏菌多价油乳剂灭活苗的研制[J].中国兽医科技,1998,28(7)：6-8
[37]崔锦鹏,颜世敢,徐培莲,等.鸡大肠杆菌多价油乳剂灭活疫苗的研制及应用[J].山东农业科学,2000,6：45-47
[38]杨小燕,沈绍新,李晓华,等.鸡致病性大肠杆菌的分离鉴定和自场灭活苗的研制[J].中国兽医杂志,1999,25(2)：23-24
[39]窦大庆,彩尼瓦尔,古丽巴哈尔,等.喀什地区鸡大肠杆菌的分离鉴定及多价灭活苗的研制[J].中国兽医杂志,2002.38(3)：19-20
[40]杨发龙.禽大肠杆菌病疫苗[J].西南民族学院学报自然科学版,2000,26(4)：422-424
[41]Gyimah J E. Immunogenicity of an Escherichia coli multivalent pilus vaccine in chickens [J]. Avian Dis,1986,30:687-689
[42]英特威.鸡大肠杆菌病及其防制[J].养禽与禽病防制,1995,11：25-26
[43]戴鼎震,李康然.禽大肠杆菌菌毛的特性及免疫原性研究[J].广西农学院学报,1992,11(2)：47-54
[44]黄淑坚,林维庆,李进红.鸡病原性大肠杆菌荚膜多糖亚单位疫苗的研究[J].中国兽医科技,1996,22(6)：50-51
[45]Korn A, Rajabi Z, Wassum B, et al. Enhancement of uptake of lipopolysaccharide in macrophages by the major outer membrane protein OmpA of Gram-negative bacteria[J]. Infect Immun,1995,63(7):2697-2705
[46]Wiertz E J, Delvig E M, Donders, et al. T-cell responses to outer membrane proteins of Neisseria meningitidis:comparative study of the opa.opc and por A proteins[J]. Infect Immun,1996,64(1):298-304
[47]赵香汝.禽大肠杆菌外膜蛋白免疫原性的研究[D].北京：北京农业大学,1998
[48]刘熙文,黄青云.禽大肠杆菌病4种弱毒菌苗免疫原性的研究[J].中国兽医杂志,1999,25(3)：21-14
[49]Frommer A, Freidlin P J, Brod R R. Experimental vaccination of young chickens with a live non-pathogenic strain of Escherichia coli[J]. Avian Pathol, 1994,23(3):425-433
[50]Abdul-Aziz T A, El-Aukhon S N. Serum sensitivity and pathogenicity for chickens and chicks embrys of Escherichia coli JS strain [J]. Vet Res,1996, 27(3):267-271
[51]Yang H C, ChenS, David G W, et al. Characterization of multiple antimicrobial resistant Escherichia coli isolates from diseased chickens and swine in China [J]. Journal of Clinical Microbiology,2004,42(8):3483-3489
[52]Murray B E. New aspects of antimicrobial resistance and resulting the therapeutic dilemmas[J]. J Infect Dis,1991,163:1185
[53]雷连成.细菌的耐药性(Ⅰ)[J].中国兽药杂志,2002,36(11)：41-44.49
[54]崔晓文,张秀英.细菌耐药性产生的分子机制与耐药基因的快速检测方法[J].中国兽药杂志,2004,38(9)：30-32
[55]沈关心.微生物学与免疫学(第5版)[M].北京：人民卫生出版社,2003,288
[56]张永利,万献尧.细菌耐药性研究进展[J].中国医师杂志,2004,6(12)：1721-1722
[57]Maneewannakul K, Levy SB. Identification for mar mutants among quinoloneresistant clinical isolates of Escherichia coli[J]. Antimicroh Agents Chemother,1996,40(7):1695-1698
[58]Mobak KDL, Baggesen FK, Aarestrup JM, et al. An outbreak of multi-drug-resistant, quinolone-resistant Salmonella enterica serotype Ty-phimurium DT104[J]. Engl Med,1999,341:1420-1425
[59]Davies J, Smith DI. Plasmid-determined resistance to antimicrobiala-gents [J]. Annd Rev Microbiol,1978,32:469-518
[60]Dorthe S, Frank MA, Lars BJ. Characterization of integrons and antibiotic resistance genes in Danish multiresistants Salmonella enterica Ty-Phimurium DT104[J]. FEMS Microbiology Letters,1998,160:37-41
[61]P Mazodier, R Petter, C Thompson. Intergeneric conjugation between E. coli and Steptomyces species [J]. J Bacteria,1989,171(6):3583-3585
[62]Farrar W E. Molecular analysis of plasmids in epidemiologic investigation [J]. J Infect Dis,1983,148(1):1
[63]P Mazodier, J Davies. Gene transfer between distantly related bacteria [J]. Annu Rev Genetics,1991,25:147-171
[64]张秀英.抗生素的耐药机制分类及概述[A].1999年中国兽医微生物学学术年会论文集[C].北京：中国微生物学会兽医微生物学专业委员会,1999：205-209
[65]张继瑜,赵荣材,邓旭明,等.喹诺酮类药物耐药性的分子机制[A].中国畜牧兽医学会—兽医药理毒理学分会第七次学术讨论会论文摘要汇编[C].北京：中国畜牧兽医学会.2000,15
[66]雷连成,韩文瑜.段艳.大肠杆菌耐药性抑制剂作用机制的初步研究[J],中国兽药杂志,2004.38(2)：18-21
[67]张永利.细菌耐药性研究进展[J].中国医师杂志,2004,6(12)：1721-1722
[68]朱力军.动物大肠杆菌耐药性的变化趋势[J].中国兽药杂志,2001,35(2)： 16-18
[69]vanden Bogaard A E, London N, Driessen C, et al. Antibiotic resistance of faecal Escherichia coli in poultry farmers and poultry slaughterers [J]. Journal of Antimicrobial Chemotherapy,2001,47:763-771
[70]柳春华,韩少礼,吕学章,等.从药敏试验的结果观察鸡大肠杆菌病的耐药性[J].黑龙江畜牧兽医,1993,11：25-26
[71]高崧,崔国搁,唐一鸣,等.我国部分地区105个禽大肠杆菌的药敏试验[J].中国畜禽传染病,1998,20(5)：300-301
[72]孙鎏国,蒋锁俊,姚德法.致病性大肠杆菌的耐药性监测[J].上海畜牧兽医通讯,2004,5：18
[73]刘栓江,杨汉春,王建肪,等.鸡源大肠杆菌的耐药性监测[J].中国兽医杂志,2004,40(6)：48-49
[74]孙海虹,马同锁,于珊,等.鸡大肠杆菌的菌株鉴定及药物敏感试验[J].河北师范大学学报(自然科学版),2005,29(6)：263-266
[75][76]雷连成,韩文瑜,郑丹.大肠杆菌流行株耐药特性对其免疫效果的影响[J].吉林农业大学学报,2005,27(5)：554-558
[76]王红宁.禽病的新特点及其防治对策和用药安全[J].中国畜牧杂志,2007,43(16)：12-15
[77]李桂喜.鸡大肠埃希氏菌血清型鉴定及药敏试验研究[J].第15届世界禽病大会论文集,2007,167
[78]潘渭涓,陈祥,王晓泉,等.1993-2008年禽源大肠杆菌和沙门菌对喹诺酮类药物耐药性分析[J].中国人兽共患病学报,2009,25(7)：630
[79]Prats G, Mirelis B, Llovet T, et al. Antibiotic resistance trends in enteropathogenic bacterial solated in 1985～1987 and 1995～1998 in Barcelona [J]. Antimicrob Agents Chemother.2000,44:1140-1145
[80]刘芳萍,李昌文,终恒敏.沙门氏菌对哇诺酮类药物耐药性的分子机制[J].中国兽医杂志,2005,41(2)：43
[81]J Rupp M E, Fey P D. Extended spectrum -Lactamase (ESBL) producing Enterobacteriaceae considerations for diagnosis.prevention and drug treatment [J]. Drugs,2003,64(4):353-365
[82]Titus A M, Msagati and Mathew M.Nindi. Determination of β-lactam residues in foodstuffs of animal origin using supported liquid membrane extraction and liquid chromatography-mass spectrometry[J]. Food Chemistry,2007,100: 836-844
[83]Blanco JE, Blanco M, Mora A, et al. Production of toxins (enterotoxins. verotoxins. and necrotoxins) and colicins by Escherichia coli strains isolated from septicemic and healthy chickens:relationship with in vivo pathogenicity[J]. J Clin Microbiol,1997,35:2953-2957
[84]Skyberg JA, Johnson TJ, Johnson JR, et al. Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli isolate enhances its abilities to kill chicken embryos. grow in human urine. and colonize the murine kidney[J]. Infect Immun,2006,74:6287-6292
[85]冯善祥.复方制剂对鸡大肠杆菌病的临床疗效观察[J].中国畜牧兽医,2011,38(2)：236-238
[86]邵泽光,丰西科,高春风.中西药治疗鸡大肠杆菌病的试验[J].中国畜禽种业,2011,1：145-147
[87]朱慧楠,毕可东,刘焕奇,等.氨苄西林混悬液对鸡大肠杆菌病的药效研究[J].安徽农业科学,2009,37(33)：16395-16397
[88]王自然,阮明华.氟苯尼考唬珀酸钠对人工诱发鸡大肠杆菌病的疗效观察[J].中国畜牧兽医,2010,37(4)：212-214.
[89]贾得和.氟苯尼考液对鸡大肠杆菌病的疗效试验[J].上海畜牧兽医通讯,2010,5：48-49
[90]王春华,李慧.氟苯尼考与三甲氧苄啶水溶性粉对试验性鸡大肠杆菌病的疗效研究[J].中国畜牧兽医,2010,37(9)：207-209.
[91]李书宏,王刚,陈庄,等.抗鸡大肠杆菌病复方中药超微粉制剂的研制及药效研究[J].中国畜牧兽医,2010,37(7)：153-157
[92]杜云良,刘彦威,韩博,等.口服头抱拉定对鸡大肠杆菌病的药效研究[J].广东农业科学,2010,3：186-188
[93]龚成珍,严作廷,胡永浩,等.禽健宝对人工感染鸡大肠杆菌肉鸡的预防保护试验[J].湖南农业科学,2010,19：25-129
[94]李树梅,张发明,李应超,等.乌梅酸枣仁提取物对人工感染鸡大肠杆菌病的防治效果[J].中国比较医学杂志,2010,20(6)：49-54
[95]傅艳萍,孙斌,来航线,等.一株拮抗放线菌发酵液对试验性鸡大肠杆菌病的疗效试验[J].中国兽医科学,2009,39(11)：990-993
[96]史同瑞,许腊梅,冯万宇,等.应用微生态制剂防治鸡大肠杆菌病效果[J].当代畜牧,2008,7：13-14.
[97]张敬礼,王双山.中草药对人工感染肉仔鸡大肠杆菌病的防治效果研究[J].安徽农业科学,2008,36(18)：7646-7647
[98]武力,沈祥广,张嘉慧.氟苯尼考水溶性粉对鸡人工感染大肠杆菌的疗效试验[J].福建畜牧兽医,2006,28(4)：17
[99]蔡玉梅,尹逊河,柴同杰,等.人工感染鸡大肠杆菌病的研究[J].中国预防兽医学报,2006,28(3)：356-358
[100]田渊,杨增岐,党如意,等.菌威克对鸡大肠杆菌病的预防和治疗试验[J].中国兽医科技,2004,34(6)：56-58.
[101]周秀红,祁克宗,张丽霞,等.不同接种途径对人工诱发鸡大肠杆菌病的影响[J].安徽农业大学学报,2005,32(4)：463-466
[102]Tivendale KA, Allen JL, Ginns CA, et al. Association of iss and iucA. but not tsh. with plasmid-mediated virulence of avian pathogenic Escherichia coli[J]. Infect Immun,2004,72:6554-6560
[103]Ginns CA, Browning GF, Benham ML, et al. Development and application of an aerosol challenge method for reproduction of avian colibacillosis[J]. Avian Pathol,1998,27:505-511
[104]Gibbs PS,Petermann SR, Wooley RE. Comparison of several challenge models for studies in avian colibacillosis[J]. Avian Dis,2004,48:751-758
[105]Brown PK,Curtiss 3rd R. Unique chromosomal regions associated with virulence of an avian pathogenic Escherichia coli strain[J]. Proc Natl Acad Sci U S A.1996.93:11149-11154
[106]Pourbakhsh SA, Dho-Moulin M, Bree A, et al. Localization of the in vivo expression of P and F1 fimbriae in chickens experimentally inoculated with pathogenic Escherichia coli[J]. Microb Pathog,1997,22:331-341
[107]Kariyawasam S, Wilkie BN, Hunter DB, et al. Systemic and mucosal antibody responses to selected cell surface antigens of avian pathogenic Escherichia coli in experimentally infected chickens[J], Avian Dis,2002,46:668-678
[108]王金莉,李丽.复方头孢噻呋对人工诱发鸡大肠杆菌病的疗效试验[J].中国兽医杂志,2010,4(12)：84-85
[109]王海花,郭宏伟,唐光武.复方盐酸恩诺沙星可溶性粉对实验性鸡大肠杆菌病的疗效试验[J].家畜生态学报,2010,31(1)：93-95
[110]赵英虎,高莉,赵恒寿.硫酸丁胺卡那霉素溶液对鸡大肠杆菌病的临床疗效试验[J].饲料工业,2007,28(8)：48-49
[111]郑雪花,田勇,张煌,等.氟苯尼考水溶性油剂对人工诱发鸡大肠杆菌病的疗效[J].河北北方学院学报(自然科学版),2007,23(6)：39-42
[112]方兰勇,姜中其.氟罗沙星的急性毒性和对鸡实验性大肠杆菌病的药效[J].兽药与饲料添加剂,2001,4：10-11
[113]张红梅.中草药防治畜禽疾病的特点和优势[J].济宁师范专科学校学报,2002,6：27-28
[114]杨淑文.32种中草药抑菌活性的比较研究[J].安徽农业科学,2011,39(3)：1361-1362,1366
[115]王德成,张翠婷.黄芩等六种中草药的体外抑菌试验[J].广东畜牧兽医科技,2010,35(6)：26-28
[116]朱智勇.几种中药制剂的体外抑菌作用研究[J].现代医药卫生,2010,26(13)：2027-2028
[117]李福娟,石学魁,张晓莉,等.苦参、黄连及其配伍的体外抑菌研究[J].牡丹江医学院学报,2010,31(3)：17-19
[118]雷连成,韩文瑜,乔红伟.大肠杆菌耐药性中药抑制剂的初步研究[J].吉林农业大学学报,2003,25(4)：429-433
[119]Weisser J. Elimination of plasmids by enoxacin and ofloacin at near inhibitory concentrations [J]. A ntimicrob Chemother,1986,18(5):575-583
[120]Sonsein SA, Baldwin JN. Loss of the penicillinase plasmid after trement of staphyloccus aureus with sodium dodecyl sulfate[J]. Bacteriol, 1972,109: 262-265
[121]关玛丽,林滢,李泽芬,等.中药娄仁对大肠杆菌(H-(B101)/P-(BR322))质粒的消除作用简报[J].中国人兽共患病杂志,1995,1：25
[122]陈群,王胜春.黄芩和黄连对大肠杆菌R质粒的实验研究[J].广东医学院报,1998,16：1-3
[123]鞠洪涛,韩文瑜,王世若,等.中草药消除大肠埃希氏菌耐药性及耐药质粒的研究[J].中国兽医科技,2000,30(3)：27-29
[124]陈群,王胜春.黄芩与止痢灵对大肠杆菌R质粒消除作用[J].中国微生态学杂志,1998,10(2)：80-82
[125]倪语星,洪秀华.细菌耐药性监测与抗感染治疗[M].北京：人民军医出版社,2002
[126]Barlocco D. Novel boronic acid derivartives as inhibitors of the AmpCp lactamase [J]. Drug Discovery Today,2001,6(17):915
[127]黄通旺,杨灏强.抑制p-内酰胺酶的中草药的筛选研究[J].汕头大学学报(自然科学版),2000,15(2):46-49,54
[128]宋战昀,冯新,韩文瑜,等.金黄色葡萄球菌norA外输泵中药耐药抑制剂的筛选[J].吉林农业大学学报,2007,29(3)：329-333
[129]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报,1995,40(20)：1901-1903
[130]Stermitz. Synergy in a medicinal plant:Antimicrobial action of berberine potentiated by 5-methoxyhydnocarpin.a multidrug pump inhibitor[J]. Applied Biological,2000,97(4):1433-1437
[131]George A M, Levy S B. Amplifiabie resistance to tetracycline chloram-phenicol and her antibiotics in Escherichia coli:involvement of anon plasmid determined efflux of tetracycline[J]. Bacteriol,1983,155(2):531-535
[132]曲宝林,张永强,关现军.中药治疗大肠杆菌效果好[J].当代畜牧,1998(3)：27
[133]杨富业,孙荣华,郑志杰.复方黄连口服液防治鸡大肠杆菌病的研究[J].河南畜牧兽医,1999,20(11)：10-11
[134]胡功政,刘冰宏,班付国,等.加味黄连解毒丸对人工感染大肠杆菌病的治疗效果[J].中国兽医杂志,1998,24(11)：46-67
[135]潘树桥,周晓利,冯喜辉,等.复方中药的制备及对肉用仔鸡大肠杆菌病的防治效果[J].中国兽医科技,2000,30(2)：37-38
[136]范开,张克家,金国星.芩柏龙胆散治疗鸡大肠杆菌并的临床效果观察[J].中西结合,2001,37(6)：30-31
[137]郭世宁,刘宗柱,李金厂,等.中药“禽菌清”防治鸡人工感染大肠杆菌病的研究观察[J].中兽医学杂志,2001,103(2)：11-12
[138]汪德刚,张志远.中药防治鸡大肠杆菌病的实验[J].养禽与禽病防治,2002(9)：14-15
[139]王自然.止泻灵对鸡大肠埃希氏菌耐药和非耐药菌株的治疗实验[J].中国兽医科技,2000,30(9)：35-36
[140]赵俊,傅德桂,沈强兵.中西药治疗大肠杆菌病对产蛋率回升的观察[J].中兽医学杂志,2000,100(3)：21-22
[141]饶茂阳,郁建生.禽痢净口服液的临床效果观察[J].中兽医医药杂志,2001,4：17-18
[142]崔锦鹏,任素芳,颜世敢,等.防治鸡白痢、禽霍乱和大肠杆菌病的中草药方剂筛选及疗效试验[J].山东农业科学,2001,3：34-35
[143]蒋丹,岳静.天南星对人工诱发鸡大肠杆菌病的药效试验[J].鞍山师范学院学报,2003,5(6)：74-76
[144]褚跃成,唐国云.中草药防治鸡病的发展趋向[J].中兽医医药杂志,1998,3：21-22
[145]高菘,刘秀梵.禽大肠杆菌病的研究进展[J].养禽与禽病防治,1999,9：18-20
[146]曾春兰,钟振国.中药抗菌作用的研究进展[J].广西中医学院学报,2006.9(1)：51-53
[147]王永芬,索江华,杨书增,等.鸡大肠杆菌病的流行病学研究进展[J].郑州牧业工程高等专科学校学报,2006,26(3)：18-20
[148]赵坤,赵恒章,王三虎.中药克痢散对鸡大肠杆菌病防治效果研究[J].中国家禽,2003,25(23)：16-18
[149]李明.清瘟止痢散对肉鸡大肠杆菌病的疗效试验[J].广东畜牧兽医科技,2006,31(4)：47-48
[150]沈永恕,吉庆云,马晓海.复方中药“禽痢康”对鸡大肠杆菌病的疗效试验[J].上海畜牧兽医通讯,2009,5：31
[151]Choi JG, Jeong SI, Ku CS, et al. Antibacterial activity of hydroxyalkenyl salicylic acids from sarcotesta of Ginkgo biloba against vancomycin-resistant Enterococcus[J]. Fitoterapia,2009,80:18-20
[152]张深固,蔡海江.新城疫与禽流感病毒等多重感染的西医化疗与中医辨证论治[J].兽医导刊,2010,7：35-37
[153]孔阳,马养民,李彦军,等.车前草提取物抗菌活性的研究[J].中国酿造,2010,10：151-153
[154]王庆银,姚庆强.丹参提取液体外抑菌活性研究[J].食品与药品,2010,12(5)：184-187
[155]马永全,于新,黄雪莲,等.南药五味子提取物的抗菌及抗氧化作用[J].食品与发酵工业,2010,36(6)：45-48
[156]傅文栋.中草药及其有效成分体外抗菌抗病毒研究进展[J].中兽医医药杂志,2006,5：66-67
[157]李树明,张凤鸣,雷燕,等.50味中药对8种畜禽病原菌抑菌对比研究[J].中兽医学杂志,2000,4：5-8
[158]Pandey R, Mishra A. Antibacterial Activities of Crude Extract of Aloe barbadensis to Clinically Isolated Bacterial Pathogens[J]. Appl. Biochem. Biotech.2010,160:1356-1361
[159]Ndhlala AR, Amoo SO, Stafford GI, et al. Antimicrobial. anti-inflammatory and mutagenic investigation of the South African tree aloe (Aloe barberae) [J]. J.Ethnopharmacol,2009,124:404-408
[160]刘志祥,曾超珍,张映辉.穿心莲提取物体外抗菌活性及稳定性的研究[J].北方园艺,2009,1：105-106
[161]Najjaa H, Neffati M, Zouari S, et al.Essential oil composition and antibacterial activity of different extracts of Allium roseum L., a North African endemic species[J]. Comptes Rendus Chimie,2007,10:820-826
[162]郭红珍,姚越红,王秋芬.大蒜抑菌作用的研究[J].安徽农业科学,2007,35(2)：414-415
[163]甄清,李静,李勇,等.锦灯笼宿萼提取物体外抗菌作用研究[J].天然产物研究与开发,2006,18：273-274
[164]宋波,刘頲,吕丽艳,等.苦参、黄芩、乌梅对金黄色葡萄球菌、大肠埃希菌和白假丝酵母菌抗菌活性的研究[J].中国微生态学杂志,2010,22(6)：507-509
[165]孔阳,马养民,李彦军,等.石榴皮粗提物抗菌活性的研究[J].食品科技,2008,9：199-201
[166]刘国生.十五年来中药抗生作用的研究概况[J].中药通报,1958,4(4)：116-120
[167]Yang LX, Liu D, Feng XF, et al. Determination of tlavone for Scutel laria baicalensis from different areas by China[J]. J Chin Mater Med,2002,27: 166-169
[168]刘丹丹,孙君社.大蒜药理作用研究概况[J].中国伤残医学,2007,15(1)：61-63
[169]刘华钢,申庆荣,刘丽敏.中药抗菌研究进展[J].时珍国医医药,2010,21(2)：463-465
[170]Guarda A, Rubilar JF, Miltz J, et al. The antimicrobial activity of microencapsulated thymol and carvacrol[J]. Int J Food Microbiol,2011, in press
[171]Politeo O, Skocibusic M, Maravic A, et al. Chemical Composition and Antimicrobial Activity of the Essential Oil of Endemic Dalmatian Black Pine (Pinus nigra ssp. dalmatica) [J]. Chem Biodivers,2011.8(3):540-547
[172]PK Tarus, PH Coombes, NR Crouch, et al. Benzo[c]phenanthridine alkaloids from stem bark of the Forest Knobwood, Zanthoxylum davyi(Rutaceae)[J]. South African Journal of Botany,2006,72(4):555-558
[173]Molatova Z, Skrivanova E, Macias B, McEwan. N.R et al. Susceptibility of Campylobacter jejuni to organic acids and monoacylglycerols[J]. Folia Microbiol(Praha),2010,55:215-220
[174]Kim KY, Davidson PM, Chung HJ. Antibacterial activity in extracts of Camellia japonica L. petals and its application to a model food system[J]. J Food Prot,2001,64:1255-1260
[175]Kong WJ, Zhao YL, Shan LM, et al. Thermochemical Studies on the Quantity-Antibacterial Effect Relationship of Four Organic Acids from Radix Isatidis on Escherichia coli Growth[J]. Biol. Pharm. Bull.,2008.31:1301-1305
[176]Cunha SC, Ferreira IMPLVO, Fernandes JO, et al. Determination of lactic. acetic. succinic and citric acids in table olives by HPLC/UV. [J]. J. Liq. Chromatogr. R. T.,2001,24:1029-1038
[177]Bozzi A, Perrin C, Austin S, et al. Quality and authenticity of commercial Aloe vera gel powders [J]. Food. Chem.,2007,103:22-30
[178]Moharregh-Khiabani D, Linker RA, Gold R, et al. Fumaric Acid and its Esters:An Emerging Treatment for Multiple Sclerosis[J]. Curr. Neuropharmacol.,2009,7:60-64
[179]Roll A, Reich K, Boer A. Use of fumaric acid esters in psoriasis[J]. Indian journal of dermatology, venereology and leprology,2007,73:133-137
[180]Kreuter A, Gambichler T, Altmeyer P, et al. Treatment of disseminated granuloma annulare with fumaric acid esters[J]. BMC Dermatol.2002,2:5
[181]Comes JE, Beelman RB. Addition of fumaric acid and sodium benzoate as an alternative method to achieve a 5-log reduction of Escherichia coli O157:H7 populations in apple cider[J]. J. Food. Protect.,2002,65:476-483
[182]李建科,马晓萍,蔡玉梅,等.人工诱发鸡大肠杆菌病的接种规律[J].中 国兽医学报,2000,4(20)：372-374
[183]霍清合.大肠杆菌病多发原因及防治[J].家禽科学,2005,3：22-23
[184]郭小清,唐莉苹,聂建超.中药复方颗粒剂救鸡宝对人工诱发鸡大肠杆菌病的疗效观察[J].兽药与饲料添加剂,2004,9(3)：10-11
[185]李世宏,杨国林,巩忠福,等.中草药复方对人工感染鸡大肠杆菌防治试验[J].中兽医医药杂志,2005,4：25-26
[186]胡功政,刘冰宏,班付国,等.中草药对人工感染雏鸡大肠杆菌病的药效研究[J].中兽医学杂志,2001,1：1-2
[187]Ginns CA, Benham ML, Adams LM, et al. Colonization of the respiratory tract by a virulent strain of avianEscherichia coli requires carriage of a conjugative plasmid[J]. Infect Immun,2000,68:1535-1541
[188]Moulin-Schouleur M, Schouler C, Tailliez P, et al. Common virulence factors and genetic relationships between O18:K1:H7 Escherichia coli isolates of human and avian origin[J]. J Clin Microbiol,2006,44:3484-3492
[189]Parreira VR, Gyles CL. A novel pathogenicity island integrated adjacent to the thrW tRNA gene of avian pathogenic Escherichia coli encodes a vacuolating autotransporter toxin[J]. Infect Immun,2003,71:5087-5096
[190]Kariyawasam S, Wilkie BN, Gyles CL. Construction. characterization, and evaluation of the vaccine potential of three genetically defined mutants of avian pathogenic Escherichia coli[J]. Avian Dis,2004,48:287-299
[191]Dozois CM, Daigle F, Curtiss 3rd R. Identification of pathogen-specific and conserved genes expressed in vivo by an avian pathogenic Escherichia coli strain[J]. Proc Natl Acad Sci U S A,2002,100:247-252
[192]Mellata M, Dho-Moulin M, Dozois CM, et al. Role of virulence factors in resistance of avian pathogenic Escherichia coli to serum and in pathogenicity [J]. Infect Immun,2003,71:536-540
[193]Lamarche MG,Dozois CM, Daigle F, et al. Inactivation of the pst system reduces the virulence of an avian pathogenic Escherichia coli O78 strain[J]. Infect Immun,2005,73:4138-4145.
[194]Lymberopoulos MH, Houle S, Daigle F, et al. Characterization of Stg fimbriae from an avian pathogenic Escherichia coli O78:K80 strain and assessment of their contribution to colonization of the chicken respiratory tract[J]. J Bacteriol,2006,188,6449-6459
[195]韦旭斌.中兽医学[M].吉林：吉林科学技术出版社,1997
[196]刘钟杰,许剑琴.中兽医学[M].北京：中国农业出版社,2002,36-115
[197]SM Lutful Kabir. Avian Colibacillosis and Salmonellosis:A Closer Look at Epidemiology. Pathogenesis. Diagnosis. Control and Public Health Concerns[J]. Int. J. Environ. Res. Public Health,2010,7:90
[198]Gyles CL. Antimicrobial resistance in selected bacteria from poultry [J]. Anim Health Res Rev,2008,9(2):149-158
[199]Smith HW, Huggins MB. Effectiveness of phages in treating experimental Escherichia coli diarrhoea in calves, piglets and lambs[J]. J. Gen. Microbiol., 1983,129,2659-2675
[200]Pucci MJ, Bronson JJ, Barrett JF. et al. Antimicrobial evaluation of nocathiacins. a thiazole peptide class of antibiotics[J]. Antimicrob. Agents Chemother.,2004,48:3697-3701
[201]Ana Oliveira, Rui Sereno, Joana Azeredo. In vivo efficiency evaluation of a phage cocktail in controlling severe colibacillosis in confined conditions and experimental poultry houses [J]. Veterinary Microbiology,2010,146:303-308
[202]Lau GL, Sieo CC, Tan WS, et al. Efficacy of a bacteriophage isolated from chickens as a therapeutic agent for colibacillosis in broiler chickens[J]. Poult Sci.,2010,89(12):2589-2596
[203]Oliveira A, Sereno R, Nicolau A. et al. The influence of the mode of administration in the dissemination of three coliphages in chickens[J]. Poult Sci.,2009,88(4):728-733
[204]Johnson RP, Gyles CL, Huff WE.et al. Bacieriophages for prophylaxis and therapy in cattle, poultry and pigs [J]. Anim Health Res Rev,2008,9(2):201 -215
[205]Wang K, Evered MD. Endotoxin stimulates drinking in rats without changing dehydrational signals controlling thirst[J]. Am J Physiol,1993,265(5 Pt 2): R1043-1051
[206]Yirmiya R. Endotoxin produces a depressive like episode in rats[J]. Brain Res, 1996,711:163-168
[207]Calpai G, Squadrito F, Altavilla D, et al. Evidence that nitric oxide modulates drinking behavior[J]. Neuropharmacology,1992,31:761-766
[208]V Raghavendra, JN Agrewala, S K Kulkarni. Role of centrally administered melatonin and inhibitors of COX and NOS in LPS-induced hyperthermia and adipsia[J]. Prostaglandins. Leukotrienes and Essential Fatty Acids,1999, 60(4):249-253
[209]袁东健,陈汝兴.破瘀通脉散对脑缺血-再灌注损伤的影响及机制探讨[J].中国中西医结合急救杂志,1999,10：445
[210]李春盛,桂培春,何新华,等.NO和iNOS在内毒素诱导的大鼠急性肺损伤的作用及大黄对其影响[J].中国急救医学,2000,2：65
[211]孙军,李景峰,姚秀娟,等.山莨菪碱对内毒素休克兔血压及NO生成的影响[J].第四军医大学学报,2000,7：189
[212]Chao WW, Kuo YH, Li WC, et al. The production of nitric oxide and prostaglandin E2 in peritoneal macrophages is inhibited by Andrographis paniculata, Angelica sinensis and Morus alba ethyl acetate fractions[J]. J Ethnopharmacol,2009,122(1):68-75
[213]ChiouWF, Chen CF. Lin JJ. Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide[J]. Br J Pharmaco,2000,129(8):1553-1560
[214]Batkhuu J, HattoriK.Takano F, et al. Supp ression of NO production in activate dmacrophages in vitro and ex vivo by neoandrographolide isolated from A. paniculata [J]. Biol Pharm Bull,2002,25(9):1169-1174
[215]Csilla Becskei. Thomas Riediger, Noemi Hernadfalvy, et al. Inhibitory effects of lipopolysaccharide on hypothalamic nuclei implicated in the control of food intake[J]. Brain. Behavior, and Immunity,2008,22:56-64
[216]Riediger T, Giannini P, Erguven E, Lutz T. Nitric oxide directly inhibits ghrelin-activated neurons of the arcuate nucleus[J]. Brain Res,2006,1125: 37-45
[217]Jansky L, Vybiral S, Pospisilova D, et al. Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever[J].1995, Neuroendocrinology,62:55-61
[218]Plata-Salaman CR, Oomura Y, Kai Y. Tumor necrosis factor and interleukin-1b:suppression of food intake by direct action in the central nervous system[J]. Brain Res,1988,448:106-114
[219]Basa NR, Wang L, Arteaga JR, et al. Bacterial lipopolysaccharide shifts fasted plasma ghrelin to postprandial levels in rats[J]. Neurosci. Lett.,2003,343: 25-28
[220]王春光,张铁,蒋桂娥.鸡大肠杆菌病血清NO. TNF-α水平检测及临床意义[J].黑龙江畜牧兽医,2010,7：86-87
[221]张涛.穿心莲的研究最新进展[J].中药材.2000.23(6)：366-368
[222]Coon JT, Ernst E. Andrographis paniculata in the treatment of up-per respiratory tract in fections:asystematic review of safety and efficacy[J]. Planta Med,2004,70(4):293-298
[223]路景涛,陈敏珠.复方黄茂提取物对细菌脂多糖诱导大鼠腹腔巨噬细胞分泌TNF-α,NO及IL-1的影响[J].安徽医药,2006,10(5)：330-331
[224]高斌,高洪,严玉霖.内毒素对兔红细胞膜磷脂含量的影响及阳离子A对其的拮抗效应[J].中国兽医学报,2006,26(4)：397-401
[225]Frede S, Fandrey J, Pagel H, et al. Erythropoietin gene expression is suppressed after lipopolysaccharide or interleukin-1 beta injections in rats[J]. Am J Physiol,1997.273:R1067-1071
[226]Tillema MS, Lorenz KL. Weiss MG, et al. Sublethal endotoxemia promotes pulmonary cytokine-induced neutrophil chemoattractant expression and neutrophil recruitment but not overt lung injury in neonatal rats[J]. Biol Neonate,2000,78:308-314
[227]Goyette RE, Key NS, Ely EW. Hematologic changes in sepsis and their therapeutic implications [J]. Semin Respir Crit Care Med,2004,25:645-659
[228]Antonella Di Mario, Mariagrazia Garzia, Fiammetta Leone. Immature platelet fraction (IPF) in hospitalized patients with neutrophilia and suspected bacterial infection[J]. Journal of Infection,2009,59:201-206
[229]Chang CF, PB Hamilton. The thrombocyte as the primary circulating phagocyte in chickens [J]. J. Reticuloendothel.Soc.,1979,25:585-590
[230]Meseguer J, M A Ngeles Estban, AR Guez. Are thrombocytes and platelets true phagocytes [J]. Microsc. Res. Tech.,2002,57:491-497
[231]George JN. Platelets [J]. Lancet,2000,355:1531-1539
[232]Jay Menaker, Ian Bebvon K Martin, Jon Mark Hirshon, et al. Marked elevation of cerebrospinal fluid white blood cell count:An unusual case of Streptococcus pneumoniae meningitis. differential diagnosis. and a brief review of current epidemiology and treatment recommendations [J]. Journal of Emergency Medicine,2005,29(1):37-41
[233]Klinger MH. Platelets and inflammation[J]. Anat. Embryol. (Berl.),1997, 196:1-11
[234]林曦.家畜病理学[M].北京：中国农业出版社,1997：8-91
[235]林曦.家畜病理学[M].北京：中国农业出版社,1997：241-242
[236]任玉红,黄素珍.肉仔鸡急性大肠杆菌病病理学观察[J].肉品卫生,1997,10：1-3
[237]蒋建新.细菌内毒素基础与临床[M].北京：人民军医出版社,2004：8
[238]Dinarello CA. Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism [J]. Int J Tissue React,1992, 4:65-75
[239]Murch SH. Local and Systemic Effects of Macrophage Cytokines in Intestinal Inflammation[J]. Nutrition,1998,14:780-783
[240]Dai Y. Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway[J]. Journal of Natural Medicines,2009,63:421-429
[241]Lynn WA, Cohen J. Adjunctive therapy for septic shock:a review of experimental approaches[J]. Clinical Infectious Diseases,1995,20:143-158
[242]Ozmen L, Pericin M, Hakimi J, et al. Interleukin 12. interferon. and tumor necrosis factor are the key cytokines of the generalized Schwartzmann reaction[J]. Journal of Experimental Medicine,1994,180:907-915
[243]Fisher CJJr, Yan SB. Protein C levels as a prognostic indicator of outcome in sepsis and related diseases[J]. Critical Care Medicine,2000.28:S49-56
[244]Mesters RM. Helterbrand J, Utterback BG, et al. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications[J]. Critical Care Medicine,2000,28:2209-2216
[245]Esmon CT. The Protein C Pathway[J]. Chest,2003,124:26S-32S
[246]Regan LM, Stearns-Kurosawa DJ, Kurosawa S, et al. The endothelial cell protein C receptor:inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors [J]. Journal of Biological Chemistry,1996,271:17499-17503
[247]Griffin JH, Hartman DL. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications[J]. Critical Care Medicine.2000,28:2209-2216
[248]裴忠绳.浅谈鸡病的辫证施治[J].中兽医医药杂志,1996,2：19-20
[249]Libby P. Simon DI. Inflammation and Thrombosis:The Clot Thickens[J]. Circulation.2001,103:1718-1720
[250]Sheeja K, Shihab PK, Kuttan G. Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata Nees[J]. Immunopharmacology and Immunotoxicology,2006,28:129-140
[251]Parichatikanond W, Suthisisang C. Dhepakson P, et al.. Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression[J]. International Immunopharmacology,2010,10(11):1361-1373
[252]Liu J, Wang ZT, Ge BX. Andrograpanin. isolated from Andrographis paniculata. exhibits anti-inflammatory property in lipopolysaccharide-induced macrophage cells through down-regulating the p38 MAPKs signaling pathways[J]. International Immunopharmacology,2008,8:951-958
[253]Gao XH, Xu XX, Pan R, et al. Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway[J]. Journal of Natural Medicines,2009,63:421-429
[254]Gao XH, Xu XX, Pan R et al. Qi-Shao-Shuang-Gan. a Combination of Astragalus membranaceus Saponins with Paeonia lactiflora Glycosides.Ameliorates Polymicrobial Sepsis Induced by Cecal Ligation and Puncture in Mice [J]. Inflammation,2011:4(1):10-21
[255]Ewers C, Janssen T, Wieler LH. Avian pathogenic Escherichia coli (APEC)[J]. Berl Munch Tierarztl Wochenschr,2003,116:381-395
[256]Dho-Moulin M, Fairbrother JM. Avian pathogenic Escherichia coli (APEC) [J]. Vet Res,1999,30:299-316
[257]Dho-Moulin M, van den Bosch JF, Girardeau JP, et al. Surface antigens from Escherichia coli 02 and 078 strains of avian origin[J]. Infect. Immun.,1990, 58:740-745
[258]Dozois CM, Fairbrother JM, Harel J, et al. Pap-and pil-related DNA sequences and other virulence determinants associated with Escherichia coli isolated from septicemic chickens and turkeys[J]. Infect. Immun.,1992,60,2648-2656
[259]van den Bosch JF, Hendriks JH, Gladigau I, et al. Identification of F11 fimbriae on chicken Escherichia coli strains[J]. Infect. Immun.,1993,61: 800-806
[260]Ellis MG, Arp LH, Lamont SJ. Serum resistance and virulence of Escherichia coli isolated from turkeys[J]. Am. J. Vet. Res.,1988,49:2034-2037
[261]Pfaff-McDonough SJ, Home SM, Giddings CW, et al. Complement resistance-related traits among Escherichia coli isolates from apparently healthy birds and birds with colibacillosis[J]. Avian Dis,2000,44:23-33
[262]Chaffer M, Heller ED, Schwartsburd B. Relationship between resistance to complement, virulence and outer membrane protein patterns in pathogenic Escherichia coli O2 isolates [J]. Vet. Microbiol.,1999,64:323-332
[263]Emery DA, Nagaraja KV, Shaw DP. et al. Virulence factors of Escherichia coli associated with colisepticemia in chickens and turkeys[J]. Avian Dis, 1992,36:504-511
[264]Blanco JE, Blanco M, Mora A, et al. Production of toxins (enterotoxins. verotoxins. and necrotoxins) and colicins by Escherichia coli strains isolated from septicemic and healthy chickens:relationship with in vivo pathogenicity[J]. J. Clin. Microbiol.,1997,35:2953-2957
[265]Parreira VR, Yano T. Cytotoxin produced by Escherichia coli isolated from chickens with swollen head syndrome (SHS) [J]. Vet. Microbiol.,1998,62: 111-119
[266]VL Waters, JH Crosa. Colicin V Virulence Plasmids[J]. Microbiological Reviews,1991,55 (3):437-450
[267]Van Alstine WG, Arp LH. Effects of Bordetella avium infection on the pulm onary clearance of Escherichia coli in tur keys[J]. Am J Vet Res,1987,48: 922-926
[268]Maina IN. Scanning electro n microscope study of the spatia 1 organization of the air and blood conductingcomponents of the avian lung (Gallus Gallus variant domesticus) [J]. Anat Rec,1988.222:145-153
[269]Jones AW, Radn. The development of the chick tert iary bronchus. I. General development and the mode of produ ction of the osmio philic inclusion body[J]. J Anat,1972,113:303-324
[270]Maina IN, King AS. The thickness of the avian bloodgas barrier:qual itati ve and quantitat ive obser vations[J]. J Anat,1982,134:553-562
[271]Qiang Shen, Robert R Rigor, Christopher D. Pivetti. Myosin light chain kinase in microvascular endothelial barrier function[J]. Cardiovascular Research, 2010,87:272-280
[272]Yuan SY. Protein kinase signaling in the modulation of microvascular permeability[J]. Vascul Pharmacol,2002,39:213-223
[273]F Moccia, S Baruffi, S Spaggiari, et al. P2Y1 and P2Y2 Receptor-Operated Ca21 Signals in Primary Cultures of Cardiac Microvascular Endothelial Cells[J]. Microvascular Research,2001,61,240-252
[274]张涛,滕可导,田启超,等.乳鼠心肌膜微血管内皮细胞的体外培养[J].解剖学报,2008,39(1)：121-123
[275]司徒镇强,吴军正.细胞培养[M].西安：世界图书出版公司,2004：81-84
[276]RS McCuskey, Renate Urbaschek, Bernhard Urbaschek. The microcirculation during endotoxemia[J]. Cardiovascula Rresearch,1996,32:752-763
[277]Andrea Nencioni, Stephen Trzeciak, Nathan I Shapiro. The microcirculation as a diagnostic and therapeutic target in sepsis[J]. Intern Emerg Med,2009, 4:413-418
[278]Lehr HA, Bittinger F, Kirkpatrick CJ. Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy [J]. J Pathol,2000,190:373-386
[279]Vallet B. Endothelial cell dysfunction and abnormal tissue perfusion[J]. Crit Care Med,2002,30(S5):229-234
[280]WO Twal, RM Leach. Isolation And Characterization of Micro Vascular Endothelial Cells From Chicken Fat Pads[J]. In Vitro Cell. Dev Biol. Animal, 1996,32:403-408
[281]David Waddington, AJ Springbett, DW Burt A Chromosome-Based Model for Estimating the Number of Conserved Segments Between Pairs of Species From Comparative Genetic Maps [J]. Genetics,2000,154 (1):323-332
[282]RPMA Crooijmans, RJM Dijkhof, Tineke Veenendaal. The Gene Orders on Human Chromosome 15 and Chicken Chromosome 10 Reveal Multiple Inter-and Intrachromosomal Rearrangements[J]. Mol. Biol. Evol.,2001,18(11): 2102-2109
[283]Adler HE, DaMassa AJ. Toxicity of endotoxin to chicks[J]. Avian Dis,1979, 23(1):174-178
[284]YB Shen, XS Piao, SW Kim, et al. The effects of berberine on the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide in broiler chickens[J]. Poult Sci.2010,89(1):13-19
[285]de Boever S, Neirinckx EA, Meyer E, et al. Pharmacodynamics of tepoxalin. sodium-salicylate and ketoprofen in an intravenous lipopolysaccharide inflammation model in broiler chickens[J]. J. vet. Pharmacol. Therap.,2010. 33:564-572
[286]De Boever S, Croubels S, Meyer E. et al. Characterization of an intravenous lipopolysaccharide inflammation model in broiler chickens[J]. Avian Pathology,2009,38:403-411
[287]RS McCuskey, Renate Urbaschek, Bernhard Urbaschek. The microcirculation during endotoxemia[J]. Cardiovascula Rresearch,1996,32:752-763
[288]Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease[J]. N Engl J Med,2000,342:1792-1801
[289]Aso Y. Fibrinolysis and cardiovascular disease in type 2 diabetes:roles of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor[J]. Future Lipidology,2006,1:429-440
[290]Fay WP, Garg N, Sunkar M. Vascular functions of the plasminogen activation system[J]. Arterioscler Thromb VascBiol,2007.27:1231-1237
[291]Sprengers ED, Kluft C. Plasminogen activator inhibitors[J]. Blood.1987. 69:381-387
[292]Zorio E, Gilabert-Estelles J, Espana F, et al. Fibrinolysis:The key to new pathogenetic mechanisms[J]. Curr Med Chem,2008,5:923-929
[293]Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: Studies of PAI-1[J]. Arterioscler Thromb Vasc Biol,1998,18:1-6
[294]Weisberg AD, Albornoz F, Griffin JP, et al. Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling[J]. Arterioscler Thromb VascBiol,2005, 25:365-371
[295]Aso Y. Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis[J]. Front Biosci,2007,12:2957-2966
[296]van Hinsbergh VW, Kooistra T, van den Berg EA, et al. Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo[J]. Blood,1988,72:1467-1473
[297]Yunzi Chen, Juan Kong, Tao Sun, et al.1.25-Dihydroxyvitamin D3 suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-KB activation[J]. Archives of Biochemistry and Biophysics,2011,507 (2):241-247
[298]Liu X, Peng YM, Liu FY, et al. Effect of indomethacin on fibronectin and plasminogen activator inhibitor-1 in cultured human peritoneal mesothelial cells[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban,2005,30(5):590-592, 603
[299]Dong J, Fujii S, Imagawa S, et al. IL-1 and IL-6 induce hepatocyte plasminogen activator inhibitor-1 expression through independent signaling pathways converging on C/EBP delta[J]. Am J Physiol Cell Physiol,2007, 292:209-215
[300]阮秋蓉,宋建新,邓仲端.山莨菪碱抗血栓形成的机制研究[J].中华病理学杂志,2000,29(3)：212-215
[301]阮秋蓉,宋建新,邓仲端.川芎嗪抗血栓形成的机制研究[J].中国动脉硬化杂志,1998,6(4)：297-300
[302]周喆.复方丹参方活性单体对TNF-α损伤人血管内皮细胞的保护作用[D].北京：中国人民解放军军事医学科学院,2005
[303]王宗仁,郑瑾,马爱玲,等.中药芪丹通脉片对动脉粥样硬化大鼠主动脉内皮细胞及PAI-1表达影响[J].第四军医大学学报,2004,25(14)：1290-1293
[304]郑培永,安德明,季光.不同治则中药复方对胆汁淤积性肝纤维化大鼠PAI-1影响的研究[J].中西医结合肝病杂志,2007,17(5)：284-287
[305]刘春生,陈和平,韩淑莲,等.利肾血冲剂对慢性肾炎血瘀型患者血清中t-PA、PAI-1的影响及临床意义[J].中医研究,2008,21(4)：28-30
[306]杨长春,马增春.黄芪、当归对血管内皮细胞纤溶酶原激活物抑制剂-1的影响[J].第三军医大学学报,2010,32(11)：1149-1151
[307]何晓峰,刘蔚,刘晓城,赵晓琴等.黄芪对左肾静脉狭窄大鼠肾组织TGF-β1和PAI-1表达的影响[J].中国组织化学与细胞化学杂志,2008,17(3)：247-251
[308]MackmanN. The many faces of tissue factor[J].J ThrombHaemost.2009. 7(S1):136-139
[309]Kasthuri RS, Taubman MB, Mackman NJ. Role of tissue factor in cancer[J]. Clin Oncol,2009,27(29):4834-4838
[310]Breitenstein A, Tanner FC, LTF Circ J. Tissue factor and cardiovascular disease:quo vadis[J].2010,74(1):3-12
[311]Gross PL, Vaezzadeh N. Tissue factor microparticles and haemophilia[J]. Thromb Res,2010,125 (SI) : 67-69
[312]Pixley RA, De La Cadena R, Page JD, et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal antifactor XII antibody to block contact activation in baboons[J]. J Clin Invest,1993,91:61-68
[313]Shimura M, Wada H, Wakita Y, et al. Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation[J]. Am J Hematol,1996,52:165-170
[314]Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis[J]. Am J Pathol,1989,134:1087-1097
[315]Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis[J]. Arterioscler Thromb Vasc Biol, 2007,27:1687-1693
[316]Pawlinski R, Tencati M, Holscher T, et al. Role of cardiac myocyte tissue factor in heart hemostasis[J]. J Thromb Haemost,2007,5:1693-1700
[317]de Ward V, Hansen HR, Spronk HH, et al. Differential expression of tissue factor mRNA and protein expression in murine sepsis. The role of the granulocyte revisited[J]. Thromb Haemost,2006,95:348-353
[318]Erlich J, Fearns C, Mathison J, et al. Lipopolysaccharide induction of tissue factor expression in rabbits [J]. Infect Immun,1999,67:2540-2546
[319]Mizumura K, Gon Y, Kumasawa F, et al. Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates lipopolysaccharide-induced tissue factor expression in pulmonary microvasculature[J]. Int Immunopharmacol, 2010,10(9):1062-1067
[320]Kim I, Oh JL, Ryu YS, et al. Angiopoietin-1 negatively regulates expression and activity of tissue factor in endothelial cells[J]. FASEB J,2002,16(1): 126-128
[321]文志斌,尚改萍,何晓凡,等.补阳还五汤对凝血酶诱导血管内皮细胞释放No、vWF、TFPI及表达组织因子的影响[J],湖南医科大学学报,2002,27(4)：315-319
[322]尚改萍,文志斌,李俊成,等.补阳还五汤对TNF-α诱导血管内皮细胞释放vWF及表达组织因子的影响[J].湖南医科大学学报,2000,25(2)：129-131
[323]何晓凡,文志斌,贺石林.四物汤对脂多糖诱导乳鼠星形胶质细胞表达组织因子的影响[J].血栓与止血学,2004,10(3)：104-106
[324]成春英,文志斌.何晓凡,等.灵芝合剂对乳鼠星形胶质细胞组织因子表达的影响[J].中国比较医学杂志,2006,16(5)：263-266
[325]张玉珠,张艳,于睿,等.益气活血复方对动脉粥样硬化家兔纤溶系统及TF的影响[J].中华中医药学刊,2009,27(11)：2333-2337
[326]汪自龙,李东野,夏勇,等.葛根素对急性冠脉综合征患者体外单核源巨噬细胞MMP-9及TF的影响[J].江苏中医药,2008,40(5)：87-88
[327]谢薇,夏凌辉,方峻,等.人参皂苷Rb1对白消安诱导人脐静脉内皮细胞表达PAI-I、TF和TGF-β1的影响[J].中国病理生理杂志,2008,24(9)：1856-1858
[328]熊石龙,文志斌,何晓凡,等.川芎嗪抑制TNF-α诱导人脐静脉血管内皮细胞组织因子表达的机制研究[J].广东医学,2008,29(4)：545-548
[329]Holp EW, Aklnnedov A, Luscher TF, et al. Berberine, a natural lipid-lowering drug, exerts prothrmnbotic effects on vascular cells[J], J Mol Cell Cardial, 2009,46(2):234-240
[330]Kaur G, Roberti M, Ralul F, et al. Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol[J]. Thromb Res,2007,119(2):247-256
[331]Li YD, Ye BQ, Zheng SX, et al. NF-kappaB transcription factor p50 critically regulates tissue factor in deep vein thrombosis [J]. J Biol Chem,2009,284(7): 4473-4483
[332]孙慧燕,孟祥艳,罗玉玉,等.Kruppel样锌指转录因子在内皮细胞中的生物学作用[J].武警医学院学报,2009,18(2)：165-168
[333]Botella LM, Sanchez-Eisner T, Sanz-Rodriguez F, et al, Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Spl and KLF6:their potential role in the response to vascular injury[J]. Blood,2002,100:4001-4010
[334]Kojima S, Hayashi S, Shimokado K, et al. Transcriptional activation of urokinase by the Kruppel-like factor Zf9/COPEB activates latent TGF-betal in vascular endothelial cells[J]. Blood.2000.95:1309-1316
[335]Kuo CT, Veselits ML. Barton KP, et al. The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis[J], Genes Dev,1997,11:2996-3006
[336]Yet SF, McA Nulty MM, Folta SC, et al. Human EZF. a Kruppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains[J]. J Biol Chem,1998,273: 1026-1031
[337]SenBanerjee S, Lin Z, Atkins GB, et al. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation[J]. J Exp Med,2004,199: 1305-1315
[338]Zhiyong Lin, Ajay Kumar, Sucharita SenBanerjee, et al. Kruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function[J]. Circ. Res.,2005, 96:48-57
[339]Dekker RJ, van Soest S, Fontijn RD, et al. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2)[J]. Blood,2002,100:1689-1698
[340]Kumar A, Lin Z, SenBanerjee S, et al. Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of MEF2 by NF-kappaB and histone deacetylases[J]. Mol Cell Biol,2005,25:5893-5903
[341]陈理国,张聪,郑仲谨,等.全身炎症反应综合证发生的分子机制研究进展[J].西南国防医药,2003,13(5)：566-569
[342]窦肇华,张远强,郭顺根.免疫细胞学与疾病[M].北京：中国医药科技出版社,2004,9：771-785
[343]张涛,黄会岭,胡格,等.小檗碱、绿原酸和黄芩苷对LPS损伤大鼠肠黏膜微血管内皮细胞表达ICAM-1的影响[J].畜牧兽医学报,2008,39(4)：499-502
[344]林红,胡格,伊鹏霏,等.黄芩苷、连翘酯苷对肺微血管内皮细胞分泌IFN-a、IFN-γ的影响[J].中国畜牧兽医,2009,36(6)：30-34
[345]解慧梅,胡格,索占伟,等.人参皂甙Rbl和黄芪多糖对微血管内皮细胞分泌NO、IL-6和TNF-α的影响[J].畜牧兽医,2006,37(9)：903-907
[346]Bochud PY, Calandra T. Pathogenesis of sepsis:new concepts and implications for future treatment [J]. Bmj,2003,326:262-266
[347]Zentella A.Manogue K, Cerami A. The role of cachectin/TNF and other cytokines in sepsis[J]. Prog Clin Biol Res,1991,367:9-24
[348]Nathan C. Points of control in inflammation[J]. Nature,2002,420:846-852
[349]Ronald JA, Ionescu CV, Rogers KA, et al. Differential regulation of transendothelial migration of THP-1 cells by ICAM-1/LFA-1 and VCAM-1/VLA-4[J]. J Leukoc Biol,2001,70:601-609
[350]Yang, Domingos NCK, M WS. Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium[J]. The Journal of Biological Chemistry,2002,277:46364-46373
[351]Madge LA, Pober JS. TNF signaling in vascular endothelial cells[J]. Exp Mol Pathol,2001,70:317-325
[352]Tracey KJ, Cerami A. Tumor necrosis factor:An updated review of its biology[J]. Crit Care Med.1993,21:S415-S422
[353]Al-Aly Z. Arterial calcification:a tumor necrosis factor-alpha mediated vascular Wnt-opathy[J], Transl Res.2008,151:233-239
[354]Strieter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-[alpha] in disease states and inflammation[J]. Crit Care Med,1993,21:S447-S463
[355]Mammen EF. Perspectives for the future [J]. Intensive Care Med,1993,19: S29-S34
[356]Pennica D, Nedwin G E, Hayflick J S, et al. Human tumour necrosis factor: precursor structure. expression and homology to lymphotoxin [J]. Nature, 1984,312(5996):724-729
[357]Vilcek J, Lee TH. Tumor necrosis factor[J]. J Biol Chem,1991,266:7313-7316
[358]Schmid EF, Binder K, Grell M, et al. Both tumor necrosis factor receptors. TNFR60 and TNFR80. are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor [alpha] [J]. Blood,1995,86: 1836-1841
[359]Miwa Morita. Shozo Yano, Toru Yamaguchi, et al. Phenylacetic Acid Stimulates Reactive Oxygen Species Generation and Tumor Necrosis Factor-a Secretion in Vascular Endothelial Cells[J]. Therapeutic Apheresis and Dialysis,2011,15(2):147-150
[360]Cendan JC, Moldawer LL, Souba WW, et al. Endotoxin-induced nitric oxide production in pulmonary artery endothelial cells is regulated by cytokines[J]. Arch Surg,1994,129:1296-1300
[361]Yiyi Hu, Xi Chen, Hong Lin, et al. Study on the antiendotoxin action of Pulsatillae Decoction using an Affymetrix rat genome array[J]. Cellular Immunology,2009,257,32-37
[362]Cendan JC, Moldawer LL, Souba WW, et al. Endotoxin-induced nitric oxide production in pulmonary artery endothelial cells is regulated by cytokines[J]. Arch Surg,1994,129:1296-1300
[363]Schmid EF, Binder K, Grell M, et al. Both tumor necrosis factor receptors. TNFR60 and TNFR80. are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor [alpha] [J]. Blood,1995,86: 1836-1841
[364]Tadaatsu Imaizumi, Hiroyuki Itaya, Kazumi Fujita, et al. Expression of Tumor Necrosis Factor-a in Cultured Human Endothelial Cells Stimulated With Lipopolysaccharide or Interleukin-1α[J]. Arterioscler Thromb Vasc Biol, 2000,20(2):410-415
[365]张云香,王家富.血管内皮细胞损伤与肿瘤坏死因子α的因果效应[J].中国临床康复,2005,9(27)：123-125
[366]Fabry Z, Waldschmidt MM, Hendrickson D, et al. Adhesion molecules on murine brain microvascular endothelial cells:Expression and regulation of ICAM-1 and Lgp 55[J]. J. Neuroimmunol.,1992,36:1-11
[367]Wong D, Dorovini-Zis K. Up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression on primary cultures of human brain microvessel endothelial cells by cytokine and lipopolysaccharide [J]. J. Neuroimmunol., 1992,39:11-22
[368]Luo X, Miao CH, Ge BX, et al. Effects of isoflurane, sevoflurane and desflurane on expression of ICAM-1 and VCAM-1 in LPS-induced rat lung microvascular endothelial cells[J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2010,39(5):464-469
[369]Fichtner F, Koslowski R, Augstein A, et al. Bleomycin induces IL-8 and ICAM-1 expression in microvascular pulmonary endothelial cells[J]. Exp Toxicol Pathol,2004,55(6):497-503
[370]Sawa Y, Ueki T, Hata M, et al. LPS-induced IL-6. IL-8. VCAM-1. and ICAM-1 expression in human lymphatic endothelium[J]. J Histochem Cytochem,2008,56(2):97-109
[371]Pressner K T, May A E, Wohn K D, et al. Molecular adhesion receptors and proteolytic cascade in vascular remodeling [J]. Thromb Hemost,1997,78(1):88
[372]Diacovo TG, Roth SJ, Buccola JM, et al. Neutrophil rolling, arrest, and transmigration across activated. surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD 18[J]. Blood.1996,88:146-157
[373]Diamond MS, Staunton DE, de Fougerolles AR, et al. ICAM-1 (CD54):A counter-receptor for Mac-1 (CDllb/CD18)et al. J Cell Biol,1990,111:3129-3139
[374]Dianzani C, Brucato L, Gallicchio M, et al. Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial cells by inhibiting ICAM-1 and VCAM-1 expression[J]. Br J Pharmacol,2008,153(6):1153-1161
[375]曲晓梅,金钟太,尚艳华,等.甘草水煎液抗炎作用的实验研究[J].实用药物与临床,2005,8(5)：14-16
[376]Chang YL, Chen CL, Kuo CL, et al. Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-kappaB pathways in TNF-alpha-activated endothelial cells[J]. Acta Pharmacol Sin,2010,31(5):546-553
[377]Xiping Z,Dijiong W, Jianfeng L, et al. Effects of Salvia miltiorrhizae on ICAM-1. TLR4. NF-kappaB and Bax proteins expression in multiple organs of rats with severe acute pancreatitis or obstructive jaundice[J]. Inflammation, 2009.32(4):218-332
[378]Philpott DJ, Yamaoka S. Invasive Shigella fexneri actives NF-KB through a lipopolysaccharide-dependent innate intracellular response and leads toll-8 expression in epithelial cells [J]. Immunol,2000,165:903-914
[379]Sun Z, Andersson R. NF-kB activation and inhibition:a review[J]. Shock, 2002,18(2):99-106
[380]Muller JM, Loms Ziegler-Heitbrock HW, Baeuerle PA. Nuclear factor kappa B a mediator of lipopolysaccharide effects[J]. Immunobiology,1993,187: 233-256
[381]Llui's E, Julia IE, Alex RM, et al. I-KB and p65 regulate the cytoplasmic shuttling of nuclear corepressors:Cross-talk between notch and NF-KB pathways [J]. Molecular Biology of the Cells,2003,14:491-494
[382]Zhang B, Shouping G, Chang C, et al. A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-KB Pathway[J]. Am J Respir Crit Care Med,2009,179(8):657-665
[383]Wang YJ, Wang JT, Fan QX, et al. Andrographolide inhibits NF-κB activation and attenuates neointimal hyperplasia in arterial restenosis[J]. Cell Research, 2007,17:933-941
[384]Chen YH, Lin SJ, Ku HH, et al. Salvianolic Acid B Attenuates VCAM-1 and ICAM-1 Expression in TNF-a-Treated Human Aortic Endothelial Cells[J]. Journal of Cellular Biochemistry,2001,82:512-521
[385]Zhang WJ, Hufnagl P, Binder BR, et al. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression[J]. Thromb Haemost,2003,90(5):904-914
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