猪圆环病毒2型诱导仔猪淋巴细胞凋亡途径的研究
|
摘要
猪圆环病毒病((Porcine circovirus disease, PCVD)主要是由猪圆环病毒2型(Porcine circovirus2, PCV2)引起的猪传染性疾病,自1991年在加拿大首次报道以来,至今世界各地已广泛传播。由于PCV2能致感染仔猪的免疫抑制,给全世界养猪业带来了巨大的损失。2008年第20届国际猪病大会上,人们已将PCVD列为当前危害养猪业发展的头号疾病。PCV2感染的主要特征是外周血和免疫器官淋巴细胞的大量缺失及单核细胞的浸润,也是其致感染仔猪免疫抑制的基础。对于PCV2致淋巴细胞缺失的机制至今尚有争论,有的研究表明是由于淋巴细胞凋亡引起的,有的则提出反对意见。本试验在我们课题组以前研究的基础上,通过体内外试验,研究PCV2导致淋巴细胞缺失的机制及其主要信号途径。
离体试验：选用5头猪圆环病毒2型及猪呼吸和繁殖综合征病毒(PRRSV)抗体阴性普通断奶仔猪,无菌分离脾脏淋巴细胞和巨噬细胞(Mφ),分别以PCV2和PCV2+Mφ与淋巴细胞相互作用,同时设Mφ和空白对照组。培养0、6、12、24h后分别收取各组淋巴细胞,用流式细胞术对细胞凋亡率进行测定,半定量RT-PCR法测定淋巴细胞Fas和FasL mRNA的转录情况,放射免疫法检测cAMP和cGMP浓度。结果：PCV2+Mcp组的淋巴细胞凋亡率在24h时显著高于其他3组(p<0.05)；6h时,PCV2+Mcp组淋巴细胞的Fas mRNA转录量显著高于空白对照组(p<0.05),24h时显著高于其他3组(p<0.05); FasL mRNA的转录变化与Fas mRNA基本一致。PCV2对细胞内cAMP和cGMP浓度影响不大,而Mφ在6h时能显著下调cAMP和cGMP浓度和cAMP/cGMP比例(p<0.05),12h时下调cGMP浓度(p<0.05),上调cAMP和cGMP比例(p<0.05)24h时上调cGMP浓度(p<0.05),但下调cAMP/cGMP比例(p<0.05)。相关性分析表明,淋巴细胞凋亡率和Fas/FasLmRNA的转录呈显著正相关(分别为：Fas,p=0.000, r=0.606; FasL,p=0.000, r=0.579).表明PCV2能诱导体外培养淋巴细胞的凋亡,且巨噬细胞能协同PCV2诱导淋巴细胞的凋亡,这种细胞凋亡的发生与Fas/FasL系统有关。
为进一步探讨在仔猪体内PCV2诱导淋巴细胞凋亡的情况及其机制,首先复制了PCVD动物模型。方法：选取19头ELISA检测PCV2抗体阴性及PCR检测PCV2病原阴性的5周龄健康断奶仔猪,随机分为对照组4头和攻毒组15头。攻毒猪每头滴鼻4mLPCV2病毒悬液并辅以佐剂刺激,对照组攻等量PCV2阴性的PK15细胞悬液。攻毒后每天观察其临床症状和测定直肠温度,并分别于0,14,21,35d扑杀。取血液分离血清,进行PCV2. PRRSV和PRV抗体滴度(ELISA法),PCV2核酸(PCR法),血清细胞色素C(ELISA法)浓度的检测；取肺脏、心脏、肝脏、肾脏、脾脏、肠系膜淋巴结、腹股沟淋巴结和支气管淋巴结等,观察肉眼和组织病理变化。结果：所有攻毒猪均出现病毒血症。组织病理学变化,在21d时最为严重,主要以出血性问质性肺炎,淋巴组织淋巴细胞缺失及巨噬细胞和嗜酸性粒细胞浸润,肝炎及肾炎为特征。血清PCV2抗体及细胞色素C浓度均随着攻毒时间的延长而显著升高,并且两者呈显著正相关。结论：成功复制出了猪圆环病毒病动物模型,且血清细胞色素C可以作为PCVD病程发展的重要监测指标。
在成功复制的PCVD模型上,选取病变最严重的两个外周免疫器官：腹股沟淋巴结和脾脏,探讨在PCV2感染过程中诱导淋巴细胞凋亡的动态变化及其主要凋亡途径。方法：取腹股沟淋巴结和脾脏,流式细胞术检测细胞凋亡率；荧光定量RT-PCR检测Fas/FasL及bcl-2/bax mRNA表达量；分光光度法检测caspase-3, caspase-8和caspase-9的活性；荧光分光光度法检测细胞内Ca2+浓度,孔雀绿比色滴定盒检测Ca2+-ATP酶的活性,荧光定量RT-PCR检测钙/钙调素依赖性磷酸激酶II mRNA相对表达量；放射免疫法检测cAMP和cGMP浓度。同时检测血清中sFas/sFasL浓度的变化。
腹股沟淋巴结试验结果：(1)细胞凋亡率：三个实验组仔猪腹股沟淋巴结的细胞凋亡率均显著高于对照组(P<0.01),并且攻毒后14d的凋亡率最高。(2)FasL mRNA水平,攻毒后21d显著高于对照组(p<0.05),Fas mRNA表达,攻毒后35d显著低于对照组(p<0.05)。(3)6cl-2和bax mRNA表达量及bax/bcl-2比值：bax mRNA表达量及bax/bcl-2比值均在14d时显著上调(p<0.05)。(4)caspase活性：caspase-3和caspase-8活性变化趋势一致,均在攻毒后21d显著高于对照组(p<0.05),其他时间与对照组相比差异不显著(p>0.05),caspase-9的活性变化不大(p>0.05)。(5)细胞内[Ca2+]和Ca2+-ATP酶活性：三个攻毒组腹股沟淋巴结细胞内[Ca2+]均显著高于对照组(p<0.01),并且21d时最高；Ca2+-ATP酶活性,21d时显著下调(p<0.05)；CaMK Ⅱ mRNA表达量在整个实验过程中变化不大。(6)cAMP和cGMP含量的变化：cGMP浓度在攻毒后21d时显著下降(p<0.05),而cAMP浓度变化不大,但三个攻毒组cAMP/cGMP比值均显著高于对照组(p<0.05)。脾脏试验结果：(1)脾脏细胞凋亡率,三个实验组均显著高于对照组(p<0.01),并且14d的凋亡率最高；(2)FasL mRNA水平,在攻毒后21d显著高于对照组(p<0.05),35d时极显著高于对照组(p<0.01)；Fas mRNA35d时的表达量显著低于对照组(P<0.05)；(3)bax mRNA的表达量,相比对照组14d时显著下降,35d时极显著升高(P<0.01),bax/bcl-2比值,14d和21d时比对照组显著下调(p<0.05)；(4)caspase-3和caspase-8活性,攻毒后均逐渐升高,三个攻毒组均极显著高于对照组(p<0.01)；caspase-9活性,相比对照组21d时极显著上升(p<0.01),35d时略有下降,但仍然显著高于对照组(p<0.05)；(5)细胞内Ca2+浓度,三个攻毒组均显著高于对照组(p<0.01),并且随着攻毒时间的延长逐渐升高；Ca2+-ATP酶活性在21d和35d时显著下降(p<0.05)；(6)CaMKⅡ mRNA表达量35d时相比对照组显著上调(p<0.05)；(7)cAMP浓度,三个攻毒组均比对照组显著下调(p<0.05),cAMP/cGMP比值,三个攻毒组相比对照组在21d和35d时均显著下调(p<0.05)。
以上结果表明：(1)PCV2可以诱导体外培养脾脏淋巴细胞的凋亡,巨噬细胞可协同PCV2诱导体外培养淋巴细胞的凋亡,这种淋巴细胞的凋亡与Fas/FasL系统有关。(2)血清细胞色素C可以作为PCVD病程发展及预后的重要监测指标。(3)Fas/FasL途径在人工感染PCV2病毒仔猪脾脏和腹股沟淋巴结淋巴细胞凋亡中起着重要的作用。(4)PCV2介导脾脏和淋巴结淋巴细胞凋亡与胞内Ca2+浓度升高有关。
Porcine circovirus type2(PCV2) was demonstrated to be a causative agent of porcine circovirus disease (PCVD) in pigs. It is all over the world since first emerged in western Canada in1991. Because the virus related with immunosuppression in pigs, it has been caused enormous loss to pig industry of whole world. At the20th international pig's disease conference in2008, people have already classified PCVD as the No.1disease endangering pig industry's development at present. Typical pathohistological findings are lymphocyte depletion of follicular and interfollicular areas together with macrophage infiltration of lymphoid tissues. The mechanism of lymphocyte depletion is in disputing, some research discovered that apoptosis is the reason of lymphocyte depletion, but others have opposite view. In an attempt to understand the mechanism of lymphocyte depletion induced by PCV2, we design vitro experiment and vivo experiment.
In vitro:Five conventional piglets with free of antibodies against PCV2and porcine reproductive and respiratory syndrome virus (PRRSV) were used for splenocytes collection. Lymphocytes and macrophages (Mφ) isolated from spleen were distributed into four groups: lymphocytes control, co-culture with Mφ with or without PCV2inoculation (PCV2+Mφ or Mφ group), and PCV2inoculation only. The apoptosis of lymphocytes was measured with flow cytometry (FCM) at0,6,12and24h post-inoculation (HPI), and Fas and Fas ligand (FasL) mRNA in the lymphocytes were evaluated by semiquantitative RT-PCR and the cAMP/cGMP concentration by radioimmunoassay at the same time. The apoptotic rate in PCV2+Mcp group was significantly higher than other groups at24h HPI (p<0.05). The expression of Fas mRNA in PCV2+Mcp group was significantly elevated at6h (p<0.05, compared with lymphocytes control) and was the highest among four groups at24h HPI. The expression of FasL in lymphocytes was the same as that of Fas. The relationship between apoptotic rate and expression of Fas and FasL mRNA was significantly positive correlation (apoptotic rate and Fas:p=0.000, r=0.606; apoptotic rate and FasL:p=0.000, r=0.579). There is no difference between the PCV2/PCV2+Mφ and control/Mφ group in any time (p>0.05). When compared with control and PCV2group, down-regulation of the cAMP/cGMP concentration and cAMP/cGMP ratio was seen in6HPI in Mφ/PCV2+Mcp group (p<0.05),and the same change of cGMP concentration in12HPI and cAMP/cGMP ratio in24HPI (p<0.05),the reverse changes of cGMP concentration in24HPI and cAMP/cGMP ratio in12HPI was seen compared with control and PCV2group (p<0.05).The results demonstrated that macrophages could mediate the surface expression of Fas/FasL on lymphocytes and increase lymphocytes apoptosis induced by PCV2in vitro.
To understand the mechanism of the apoptosis of lymphocytes in vivo, we producted PCVD by PCV2infection. Method:nineteen piglets without antibody to PCV2and PCV2nucleic acid were allotted into four groups:a control group of four piglets, and three experimental groups of five piglets per group and sacrificed at0,14,21, or35DPI with PCV2. The clinical signs of the pigs were observed every day.The level of andibody to PCV2, cytochrome C concentration and PCV2nucleic acid in serum was detected by ELISA and PCR. Samples of the following tissues were collected:liver, kidney, heart, lung and lymphoid tissue inclouding spleen, mesenteric lymph node, inguinal lymph nodes and bronchial lymph nodes. Tissues were fixed in10%neutral buffered formalin, embedded in paraffin wax, and stained with haematoxylin and eosin (HE) for microscopic study. Results: significant up-regulation of the andibody to PCV2and cytochrome C concentration was tested when compared with the control group, and the positive correlations between the level of andibody against PCV2and cytochrome C concentration in sera. All the piglets from the three experimental groups were sufferd from viremia. The most severity pathological change was lymphoid depletion of follicular and interfollicular areas together with macrophages and eosinophilic granulocytes infiltration of lymphoid tissues and the granulomatous inflammatory reaction in lung and liver especially at21and35DPI. Conclusion:PCVD was reproducted by PCV2infection (21DPI and35DPI). Cytochrome C could be an indicator of PCVD in vivo.
When successful reproduced of PCVD, we researched the mechanism of the apoptosis induced by PCV2in the most significance periphery immune organ:inguinal lymph nodes and spleen in vivo. Method:The apoptotic rates of lymphocytes were detected with flow cytometry, the transcriptions of Fas/FasL, bax/bcl-2and CaMK II mRNA were tested by semiquantitative RT-PCR, caspase-3,-8and-9activities were measured with spectrophotometry, the cytosolic Ca2+concentrations were evaluated with spectrofluorometry, activities of Ca2+-ATPase were determined by malachite green colorimetric assay and concentrations of the cAMP/cGMP were evaluated by radioimmunity in inguinal lymph nodes and spleens, as well as the levels of sFas/sFasL were also detected in serum.
Results in inguinal lymph nodes:(1) PCV2infection was found to be associated with apoptosis of porcine inguinal lymph nodes, and the apoptosis of inguinal lymph nodes in three experimental groups (14,21, and35DPI) was significantly higher than in the control group (0DPI)(p<0.01).(2) Transcription of the FasL mRNA was upregulated by PCV2infection, particularly at21and35DPI; The transcription of Fas mRNA were down-regulated in35DPI (p<0.05).(3) The transcription of bax mRNA and bax/bcl-2ratio were up-regulated in14DPI (p<0.05).(4) The activities of caspase-3and caspase-8were obviously increased at21DPI and no significant changes at14,35DPI.(5) Significant up-regulation of cytosolic Ca2+concentration was seen when compared with the control group (p<0.01) and was highest at21d. The activities of Ca2+-ATPase were seen down-regulation in21DPI when compared with the control group (p<0.01). No statistical significant difference was observed in the transcription of CaMKⅡmRNA (p>0.05).(6) The concentrations of cAMP and cGMP were no statistical significant difference between the three experimental groups and the control group(p>0.05), but up-regulation for the cAMP/cGMP ratio was seen in all the experimental groups(p<0.05).
Results in spleen:(1) The apoptotic rates of spleen in three experimental groups were significantly higher than in the control group (0DPI)(p<0.01).(2) Expressions of the FasL mRNA were upregulated by PCV2infection, particularly at21and35DPI; but expressions of the Fas mRNA were down-regulated at35DPI.(3) The transcriptions of bax mRNA were downregulated at14DPI (p<0.05), but they were increased at35DPI (p<0.05). Bax/bcl-2ratiowas detected obvious decreasing (p<0.05) at14and21DPI.(4) The activities of caspase-3and caspase-8were gradually increased after PCV2infection and were significant up-regulation than control group (p<0.01). The activities of Caspase-9were obviously upregulated at21DPI, then were slightly depressed at35DPI, but were higher than control group (p<0.05).(5) The concentration of cytosolic Ca2+were significantly up-regulated in three experiment groups at p<0.01, and were gradually heighteded after PCV2infection. The activities of Ca2+-ATPase at21and35DPI were lower than the control group (p<0.01).(6) The relative levels of CaMKⅡmRNA were significantly up-regulated at35DPI (p<0.05).(7) The concentrations of cAMP in the three experiment groups were lower than control group(p<0.05), and cAMP/cGMP ratio were also decreased especially at21and35DPI.
The data presented above indicate that:(1) PCV2could induce apoptosis of splenic lymphocytes and macrophages could increase the apoptosis in vitro, and the apoptosis is related to Fas/FasL pathway.(2) Cytochrome C in serum could be an indicator of the development PCVD in vivo.(3) Fas/FasL pathways are very important to the apoptosis of lymphcytes induced by PCV2both in vitro and in vivo.(4) The apoptosis of lymphcytes in inguinal lymph nodes and spleen induced by PCV2are related to the cytosolic Ca2+concentration.
离体试验：选用5头猪圆环病毒2型及猪呼吸和繁殖综合征病毒(PRRSV)抗体阴性普通断奶仔猪,无菌分离脾脏淋巴细胞和巨噬细胞(Mφ),分别以PCV2和PCV2+Mφ与淋巴细胞相互作用,同时设Mφ和空白对照组。培养0、6、12、24h后分别收取各组淋巴细胞,用流式细胞术对细胞凋亡率进行测定,半定量RT-PCR法测定淋巴细胞Fas和FasL mRNA的转录情况,放射免疫法检测cAMP和cGMP浓度。结果：PCV2+Mcp组的淋巴细胞凋亡率在24h时显著高于其他3组(p<0.05)；6h时,PCV2+Mcp组淋巴细胞的Fas mRNA转录量显著高于空白对照组(p<0.05),24h时显著高于其他3组(p<0.05); FasL mRNA的转录变化与Fas mRNA基本一致。PCV2对细胞内cAMP和cGMP浓度影响不大,而Mφ在6h时能显著下调cAMP和cGMP浓度和cAMP/cGMP比例(p<0.05),12h时下调cGMP浓度(p<0.05),上调cAMP和cGMP比例(p<0.05)24h时上调cGMP浓度(p<0.05),但下调cAMP/cGMP比例(p<0.05)。相关性分析表明,淋巴细胞凋亡率和Fas/FasLmRNA的转录呈显著正相关(分别为：Fas,p=0.000, r=0.606; FasL,p=0.000, r=0.579).表明PCV2能诱导体外培养淋巴细胞的凋亡,且巨噬细胞能协同PCV2诱导淋巴细胞的凋亡,这种细胞凋亡的发生与Fas/FasL系统有关。
为进一步探讨在仔猪体内PCV2诱导淋巴细胞凋亡的情况及其机制,首先复制了PCVD动物模型。方法：选取19头ELISA检测PCV2抗体阴性及PCR检测PCV2病原阴性的5周龄健康断奶仔猪,随机分为对照组4头和攻毒组15头。攻毒猪每头滴鼻4mLPCV2病毒悬液并辅以佐剂刺激,对照组攻等量PCV2阴性的PK15细胞悬液。攻毒后每天观察其临床症状和测定直肠温度,并分别于0,14,21,35d扑杀。取血液分离血清,进行PCV2. PRRSV和PRV抗体滴度(ELISA法),PCV2核酸(PCR法),血清细胞色素C(ELISA法)浓度的检测；取肺脏、心脏、肝脏、肾脏、脾脏、肠系膜淋巴结、腹股沟淋巴结和支气管淋巴结等,观察肉眼和组织病理变化。结果：所有攻毒猪均出现病毒血症。组织病理学变化,在21d时最为严重,主要以出血性问质性肺炎,淋巴组织淋巴细胞缺失及巨噬细胞和嗜酸性粒细胞浸润,肝炎及肾炎为特征。血清PCV2抗体及细胞色素C浓度均随着攻毒时间的延长而显著升高,并且两者呈显著正相关。结论：成功复制出了猪圆环病毒病动物模型,且血清细胞色素C可以作为PCVD病程发展的重要监测指标。
在成功复制的PCVD模型上,选取病变最严重的两个外周免疫器官：腹股沟淋巴结和脾脏,探讨在PCV2感染过程中诱导淋巴细胞凋亡的动态变化及其主要凋亡途径。方法：取腹股沟淋巴结和脾脏,流式细胞术检测细胞凋亡率；荧光定量RT-PCR检测Fas/FasL及bcl-2/bax mRNA表达量；分光光度法检测caspase-3, caspase-8和caspase-9的活性；荧光分光光度法检测细胞内Ca2+浓度,孔雀绿比色滴定盒检测Ca2+-ATP酶的活性,荧光定量RT-PCR检测钙/钙调素依赖性磷酸激酶II mRNA相对表达量；放射免疫法检测cAMP和cGMP浓度。同时检测血清中sFas/sFasL浓度的变化。
腹股沟淋巴结试验结果：(1)细胞凋亡率：三个实验组仔猪腹股沟淋巴结的细胞凋亡率均显著高于对照组(P<0.01),并且攻毒后14d的凋亡率最高。(2)FasL mRNA水平,攻毒后21d显著高于对照组(p<0.05),Fas mRNA表达,攻毒后35d显著低于对照组(p<0.05)。(3)6cl-2和bax mRNA表达量及bax/bcl-2比值：bax mRNA表达量及bax/bcl-2比值均在14d时显著上调(p<0.05)。(4)caspase活性：caspase-3和caspase-8活性变化趋势一致,均在攻毒后21d显著高于对照组(p<0.05),其他时间与对照组相比差异不显著(p>0.05),caspase-9的活性变化不大(p>0.05)。(5)细胞内[Ca2+]和Ca2+-ATP酶活性：三个攻毒组腹股沟淋巴结细胞内[Ca2+]均显著高于对照组(p<0.01),并且21d时最高；Ca2+-ATP酶活性,21d时显著下调(p<0.05)；CaMK Ⅱ mRNA表达量在整个实验过程中变化不大。(6)cAMP和cGMP含量的变化：cGMP浓度在攻毒后21d时显著下降(p<0.05),而cAMP浓度变化不大,但三个攻毒组cAMP/cGMP比值均显著高于对照组(p<0.05)。脾脏试验结果：(1)脾脏细胞凋亡率,三个实验组均显著高于对照组(p<0.01),并且14d的凋亡率最高；(2)FasL mRNA水平,在攻毒后21d显著高于对照组(p<0.05),35d时极显著高于对照组(p<0.01)；Fas mRNA35d时的表达量显著低于对照组(P<0.05)；(3)bax mRNA的表达量,相比对照组14d时显著下降,35d时极显著升高(P<0.01),bax/bcl-2比值,14d和21d时比对照组显著下调(p<0.05)；(4)caspase-3和caspase-8活性,攻毒后均逐渐升高,三个攻毒组均极显著高于对照组(p<0.01)；caspase-9活性,相比对照组21d时极显著上升(p<0.01),35d时略有下降,但仍然显著高于对照组(p<0.05)；(5)细胞内Ca2+浓度,三个攻毒组均显著高于对照组(p<0.01),并且随着攻毒时间的延长逐渐升高；Ca2+-ATP酶活性在21d和35d时显著下降(p<0.05)；(6)CaMKⅡ mRNA表达量35d时相比对照组显著上调(p<0.05)；(7)cAMP浓度,三个攻毒组均比对照组显著下调(p<0.05),cAMP/cGMP比值,三个攻毒组相比对照组在21d和35d时均显著下调(p<0.05)。
以上结果表明：(1)PCV2可以诱导体外培养脾脏淋巴细胞的凋亡,巨噬细胞可协同PCV2诱导体外培养淋巴细胞的凋亡,这种淋巴细胞的凋亡与Fas/FasL系统有关。(2)血清细胞色素C可以作为PCVD病程发展及预后的重要监测指标。(3)Fas/FasL途径在人工感染PCV2病毒仔猪脾脏和腹股沟淋巴结淋巴细胞凋亡中起着重要的作用。(4)PCV2介导脾脏和淋巴结淋巴细胞凋亡与胞内Ca2+浓度升高有关。
Porcine circovirus type2(PCV2) was demonstrated to be a causative agent of porcine circovirus disease (PCVD) in pigs. It is all over the world since first emerged in western Canada in1991. Because the virus related with immunosuppression in pigs, it has been caused enormous loss to pig industry of whole world. At the20th international pig's disease conference in2008, people have already classified PCVD as the No.1disease endangering pig industry's development at present. Typical pathohistological findings are lymphocyte depletion of follicular and interfollicular areas together with macrophage infiltration of lymphoid tissues. The mechanism of lymphocyte depletion is in disputing, some research discovered that apoptosis is the reason of lymphocyte depletion, but others have opposite view. In an attempt to understand the mechanism of lymphocyte depletion induced by PCV2, we design vitro experiment and vivo experiment.
In vitro:Five conventional piglets with free of antibodies against PCV2and porcine reproductive and respiratory syndrome virus (PRRSV) were used for splenocytes collection. Lymphocytes and macrophages (Mφ) isolated from spleen were distributed into four groups: lymphocytes control, co-culture with Mφ with or without PCV2inoculation (PCV2+Mφ or Mφ group), and PCV2inoculation only. The apoptosis of lymphocytes was measured with flow cytometry (FCM) at0,6,12and24h post-inoculation (HPI), and Fas and Fas ligand (FasL) mRNA in the lymphocytes were evaluated by semiquantitative RT-PCR and the cAMP/cGMP concentration by radioimmunoassay at the same time. The apoptotic rate in PCV2+Mcp group was significantly higher than other groups at24h HPI (p<0.05). The expression of Fas mRNA in PCV2+Mcp group was significantly elevated at6h (p<0.05, compared with lymphocytes control) and was the highest among four groups at24h HPI. The expression of FasL in lymphocytes was the same as that of Fas. The relationship between apoptotic rate and expression of Fas and FasL mRNA was significantly positive correlation (apoptotic rate and Fas:p=0.000, r=0.606; apoptotic rate and FasL:p=0.000, r=0.579). There is no difference between the PCV2/PCV2+Mφ and control/Mφ group in any time (p>0.05). When compared with control and PCV2group, down-regulation of the cAMP/cGMP concentration and cAMP/cGMP ratio was seen in6HPI in Mφ/PCV2+Mcp group (p<0.05),and the same change of cGMP concentration in12HPI and cAMP/cGMP ratio in24HPI (p<0.05),the reverse changes of cGMP concentration in24HPI and cAMP/cGMP ratio in12HPI was seen compared with control and PCV2group (p<0.05).The results demonstrated that macrophages could mediate the surface expression of Fas/FasL on lymphocytes and increase lymphocytes apoptosis induced by PCV2in vitro.
To understand the mechanism of the apoptosis of lymphocytes in vivo, we producted PCVD by PCV2infection. Method:nineteen piglets without antibody to PCV2and PCV2nucleic acid were allotted into four groups:a control group of four piglets, and three experimental groups of five piglets per group and sacrificed at0,14,21, or35DPI with PCV2. The clinical signs of the pigs were observed every day.The level of andibody to PCV2, cytochrome C concentration and PCV2nucleic acid in serum was detected by ELISA and PCR. Samples of the following tissues were collected:liver, kidney, heart, lung and lymphoid tissue inclouding spleen, mesenteric lymph node, inguinal lymph nodes and bronchial lymph nodes. Tissues were fixed in10%neutral buffered formalin, embedded in paraffin wax, and stained with haematoxylin and eosin (HE) for microscopic study. Results: significant up-regulation of the andibody to PCV2and cytochrome C concentration was tested when compared with the control group, and the positive correlations between the level of andibody against PCV2and cytochrome C concentration in sera. All the piglets from the three experimental groups were sufferd from viremia. The most severity pathological change was lymphoid depletion of follicular and interfollicular areas together with macrophages and eosinophilic granulocytes infiltration of lymphoid tissues and the granulomatous inflammatory reaction in lung and liver especially at21and35DPI. Conclusion:PCVD was reproducted by PCV2infection (21DPI and35DPI). Cytochrome C could be an indicator of PCVD in vivo.
When successful reproduced of PCVD, we researched the mechanism of the apoptosis induced by PCV2in the most significance periphery immune organ:inguinal lymph nodes and spleen in vivo. Method:The apoptotic rates of lymphocytes were detected with flow cytometry, the transcriptions of Fas/FasL, bax/bcl-2and CaMK II mRNA were tested by semiquantitative RT-PCR, caspase-3,-8and-9activities were measured with spectrophotometry, the cytosolic Ca2+concentrations were evaluated with spectrofluorometry, activities of Ca2+-ATPase were determined by malachite green colorimetric assay and concentrations of the cAMP/cGMP were evaluated by radioimmunity in inguinal lymph nodes and spleens, as well as the levels of sFas/sFasL were also detected in serum.
Results in inguinal lymph nodes:(1) PCV2infection was found to be associated with apoptosis of porcine inguinal lymph nodes, and the apoptosis of inguinal lymph nodes in three experimental groups (14,21, and35DPI) was significantly higher than in the control group (0DPI)(p<0.01).(2) Transcription of the FasL mRNA was upregulated by PCV2infection, particularly at21and35DPI; The transcription of Fas mRNA were down-regulated in35DPI (p<0.05).(3) The transcription of bax mRNA and bax/bcl-2ratio were up-regulated in14DPI (p<0.05).(4) The activities of caspase-3and caspase-8were obviously increased at21DPI and no significant changes at14,35DPI.(5) Significant up-regulation of cytosolic Ca2+concentration was seen when compared with the control group (p<0.01) and was highest at21d. The activities of Ca2+-ATPase were seen down-regulation in21DPI when compared with the control group (p<0.01). No statistical significant difference was observed in the transcription of CaMKⅡmRNA (p>0.05).(6) The concentrations of cAMP and cGMP were no statistical significant difference between the three experimental groups and the control group(p>0.05), but up-regulation for the cAMP/cGMP ratio was seen in all the experimental groups(p<0.05).
Results in spleen:(1) The apoptotic rates of spleen in three experimental groups were significantly higher than in the control group (0DPI)(p<0.01).(2) Expressions of the FasL mRNA were upregulated by PCV2infection, particularly at21and35DPI; but expressions of the Fas mRNA were down-regulated at35DPI.(3) The transcriptions of bax mRNA were downregulated at14DPI (p<0.05), but they were increased at35DPI (p<0.05). Bax/bcl-2ratiowas detected obvious decreasing (p<0.05) at14and21DPI.(4) The activities of caspase-3and caspase-8were gradually increased after PCV2infection and were significant up-regulation than control group (p<0.01). The activities of Caspase-9were obviously upregulated at21DPI, then were slightly depressed at35DPI, but were higher than control group (p<0.05).(5) The concentration of cytosolic Ca2+were significantly up-regulated in three experiment groups at p<0.01, and were gradually heighteded after PCV2infection. The activities of Ca2+-ATPase at21and35DPI were lower than the control group (p<0.01).(6) The relative levels of CaMKⅡmRNA were significantly up-regulated at35DPI (p<0.05).(7) The concentrations of cAMP in the three experiment groups were lower than control group(p<0.05), and cAMP/cGMP ratio were also decreased especially at21and35DPI.
The data presented above indicate that:(1) PCV2could induce apoptosis of splenic lymphocytes and macrophages could increase the apoptosis in vitro, and the apoptosis is related to Fas/FasL pathway.(2) Cytochrome C in serum could be an indicator of the development PCVD in vivo.(3) Fas/FasL pathways are very important to the apoptosis of lymphcytes induced by PCV2both in vitro and in vivo.(4) The apoptosis of lymphcytes in inguinal lymph nodes and spleen induced by PCV2are related to the cytosolic Ca2+concentration.
引文
[1]Gillespie, J, Opriessnig, T, Meng, X J, Pelzer, KBuechner-Maxwell, V. Porcine Circovirus Type 2 and Porcine Circovirus-Associated Disease[J]. J Vet Intern Med,2009,
[2]Harding, J C. The clinical expression and emergence of porcine circovirus 2[J]. Vet Microbiol, 2004,98(2):131-135
[3]Chae, C. A review of porcine circovirus 2-associated syndromes and diseases[J]. Vet J,2005, 169(3):326-336
[4]蒋大良,余兴龙.猪圆环病毒2型致病机制研究进展[J].动物医学进展,2009,30(4)：94-98
[5]熊丕华,于雷.猪圆环病毒2型(PCV2)的致病机理[J].中国畜禽种业,2009,6：145-148
[6]Segales, J, Rosell, CDomingo, M. Pathological findings associated with naturally acquired porcine circovirus type 2 associated disease[J]. Vet Microbiol,2004,98(2):137-149
[7]史利军,任林柱,李刚.猪圆环病毒2型免疫抑制机理研究进展[J].动物医学进展,2009,30(3)：74-77
[8]Ellis, J A, Bratanich, A, Clark, E G, Allan, G, Meehan, B, Haines, D M, Harding, J, West, K H, Krakowka, S, Konoby, C, Hassard, L, Martin, KMcneilly, F. Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome[J]. J Vet Diagn Invest,2000,12(1):21-27
[9]Larochelle, R, Magar, RD'allaire, S. Comparative serologic and virologic study of commercial swine herds with and without postweaning multisystemic wasting syndrome[J]. Can J Vet Res, 2003,67(2):114-120
[10]Staebler, S, Sydler, T, Buergi, E, Mccullough, K, Mcneilly, F, Allan, GPospischil, A. PMWS:an emerging disease identified in archived porcine tissues[J]. Vet J,2005,170(1):132-134
[11]Chae, C. Postweaning multisystemic wasting syndrome:a review of aetiology, diagnosis and pathology[J]. Vet J,2004,168(1):41-49
[12]郎洪武,张广川,吴发权.猪断奶后多系统衰弱综合征的血清抗体检测[J].中国兽医科技,2000,30(3)：3-5
[13]赵东升,刘有昌,安福生,李祥健.近年来我国猪圆环病毒病的流行状况及分析[J].养猪,2009.1：57-59
[14]Ellis, J, Clark, E, Haines, D, West, K, Krakowka, S, Kennedy, SAllan, G M. Porcine circovirus-2 and concurrent infections in the field[J]. Vet Microbiol,2004,98(2):159-163
[15]Quintana, J, Segales, J, Rosell, C, Calsamiglia, M, Rodriguez-Arrioja, G M, Chianini, F, Folch, J M, Maldonado, J, Canal, M, Plana-Duran, JDomingo, M. Clinical and pathological observations on pigs with postweaning multisystemic wasting syndrome[J]. Vet Rec,2001,149(12):357-361
[16]赵浩军,王先炜,姜平,范伟兴,李晓成黄保续PMWS患病猪群中PCV2与CSFV、PPV, PRRSV混合感染的调查[J].畜牧与兽医,2007,39(3)：32-35
[17]Sanchez, R E, Jr., Meerts, P, Nauwynck, H JPensaert, M B. Change of porcine circovirus 2 target cells in pigs during development from fetal to early postnatal life[J]. Vet Microbiol,2003,95(1-2): 15-25
[18]邓云波,徐飞良,申玉仁.警惕专攻动物防御功能的病毒作祟[J].中国动物保健,2007,104：56-59
[19]Krakowka, S, Ellis, J, Mcneilly, F, Waldner, C, Rings, D MAllan, G. Mycoplasma hyopneumoniae bacterins and porcine circovirus type 2 (PCV2) infection:induction of postweaning multisystemic wasting syndrome (PMWS) in the gnotobiotic swine model of PCV2-associated disease[J]. Can Vet J,2007,48(7):716-724
[20]Lorincz, M, Csagola, A, Biksi, I, Szeredi, L, Dan, ATuboly, T. Detection of porcine circovirus in rodents-Short communication[J]. Acta Vet Hung,2010,58(2):265-268
[21]张骞.种猪场圆环病毒2型的血清学调查分析[J].疫情报告,2009,3(239)：60-61
[22]Allan, GM, Mcneilly, F, Cassidy, J P, Reilly, G A, Adair, B, Ellis, W AMcnulty, M S. Pathogenesis of porcine circovirus; experimental infections of colostrum deprived piglets and examination of pig foetal material[J]. Vet Microbiol,1995,44(1):49-64
[23]尹业师,黄伟坚,陈琼,刘海鹏,谢丽华,冯建远.猪圆环病毒感染的病理组织学和致病机理研究进展[J].动物医学进展,2006,27(11)：18-21
[24]Segales, J, Allan, G MDomingo, M. Porcine circovirus diseases[J]. Anim Health Res Rev,2005, 6(2):119-142
[25]Segales,J, Domingo, M, Chianini, F, Majo, N, Dominguez, J, Darwich, LMateu, E. Immunosuppression in postweaning multisystemic wasting syndrome affected pigs[J]. Vet Microbiol,2004,98(2):151-158
[26]Bolin, S R, Stoffregen, W C, Nayar, G PHamel, a L. Postweaning multisystemic wasting syndrome induced after experimental inoculation of cesarean-derived, colostrum-deprived piglets with type 2 porcine circovirus [J]. J Vet Diagn Invest,2001,13(3):185-194
[27]冷和平,温育铭,罗瑞国,邱江.生长猪散发性圆环病毒病的综合防治研究[J].养猪,2007,6：59-62
[28]韦英益,黄伟坚,尹业师,黄广顺,覃继顺.断奶仔猪多系统衰竭综合症的病理组织学观察[J].广西农业生物科学,2007,26：70-73
[29]王海花,李艳玲,汪德刚,张桂云.猪圆环病毒的研究进展[J].家畜生态学报,2006,27(4)： 110-112
[30]施兆红,王志远,刘洪波,韩惠利,施旅娟,张书霞.山东潍坊地区PMWS临床病例的病理学研究[J].畜牧与兽医,2007,39(5)：21-23
[31]冷和平.猪圆环病毒2型致病机理及防控措施研究的回顾和展望[J].猪业科学,2008,8：84-88
[32]Allan, G MEllis, J A. Porcine circoviruses:a review[J]. J Vet Diagn Invest,2000,12(1):3-14
[33]唐宁,吕艳丽,郭鑫,杨汉春,董军,司兴奎,王忠田.仔猪人工感染猪圆环病毒2型后的病理学特征[J].中国兽医杂志,2007,43(7)：19-20
[34]Wellenberg, G J, Stockhofe-Zurwieden, N, Boersma, W J, De Jong, M FElbers, a R. The presence of co-infections in pigs with clinical signs of PMWS in The Netherlands:a case-control study[J]. Res Vet Sci,2004,77(2):177-184
[35]Segales, JDomingo, M. Postweaning multisystemic wasting syndrome (PMWS) in pigs. A review[J]. Vet Q,2002,24(3):109-124
[36]Chianini, F, Majo, N, Segales, J, Dominguez, JDomingo, M. Immunohistochemical characterisation of PCV2 associate lesions in lymphoid and non-lymphoid tissues of pigs with natural postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol, 2003,94(1-2):63-75
[37]孙运.PCV2感染仔猪急性期蛋白的变化[D].南京：南京农业大学,2009：29-38.
[38]Sarli, G, Mandrioli, L, Panarese, S, Brunetti, B, Segales, J, Dominguez, JMarcato, P S. Characterization of interstitial nephritis in pigs with naturally occurring postweaning multisystemic wasting syndrome [J]. Vet Pathol,2008,45(1):12-18
[39]Seeliger, F A, Brugmann, M L, Kruger, L, Greiser-Wilke, I, Verspohl, J, Segales, JBaumgartner, W. Porcine circovirus type 2-associated cerebellar vasculitis in postweaning multisystemic wasting syndrome (PMWS)-affected pigs[J]. Vet Pathol,2007,44(5):621-634
[40]Darwich, L, Pie, S, Rovira, A, Segales, J, Domingo, M, Oswald, I PMateu, E. Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisystemic wasting syndrome[J]. J Gen Virol,2003,84(Pt 8):2117-2125
[41]Segales, J, Pastor, J, Cuenca, RDomingo, M. Haematological parameters in postweaning multisystemic wasting syndrome-affected pigs[J]. Vet Rec,2000,146(23):675-676
[42]Rosell, C, Segales, J, Plana-Duran, J, Balasch, M, Rodriguez-Arrioja, G M, Kennedy, S, Allan, G M, Mcneilly, F, Latimer, K SDomingo, M. Pathological, immunohistochemical, and in-situ hybridization studies of natural cases of postweaning multisystemic wasting syndrome (PMWS) in pigs[J]. J Comp Pathol,1999,120(1):59-78
[43]Calsamiglia, M, Segales, J, Quintana, J, Rosell, CDomingo, M. Detection of porcine circovirus types 1 and 2 in serum and tissue samples of pigs with and without postweaning multisystemic wasting syndrome[J]. J Clin Microbiol,2002,40(5):1848-1850
[44]王忠田,杨汉春.猪圆环病2型在PMWS患猪体内分布的初步研究[J].中国兽药杂志,2007,43(1)：23-25
[45]Mcintosh, K A, Tumber, A, Harding, J C, Krakowka, S, Ellis, J AHill, J E. Development and validation of a SYBR green real-time PCR for the quantification of porcine circovirus type 2 in serum, buffy coat, feces, and multiple tissues[J]. Vet Microbiol,2009,133(1-2):23-33
[46]Kennedy, S, Moffett, D, Mcneilly, F, Meehan, B, Ellis, J, Krakowka, SAllan, G M. Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus[J]. J Comp Pathol,2000, 122(1):9-24
[47]Park, J S, Ha, Y, Kwon, B, Cho, K D, Lee, B HChae, C. Detection of porcine circovirus 2 in mammary and other tissues from experimentally infected sows[J]. J Comp Pathol,2009,140(2-3): 208-211
[48]Mateusen, B, Maes, D G, Van Soom, A, Lefebvre, DNauwynck, H J. Effect of a porcine circovirus type 2 infection on embryos during early pregnancy[J]. Theriogenology,2007,68(6):896-901
[49]Opriessnig, T, Patterson, a R, Meng, X JHalbur, P G. Porcine circovirus type 2 in muscle and bone marrow is infectious and transmissible to naive pigs by oral consumption[J]. Vet Microbiol,2009, 133(1-2):54-64
[50]Segales, J, Calsamiglia, M, Olvera, A, Sibila, M, Badiella, LDomingo, M. Quantification of porcine circovirus type 2 (PCV2) DNA in serum and tonsillar, nasal, tracheo-bronchial, urinary and faecal swabs of pigs with and without postweaning multisystemic wasting syndrome (PMWS)[J], Vet Microbiol,2005,111(3-4):223-229
[51]梁红虎,罗满林,刘镇明.PCR对猪全血、血清、尿液和粪便中PCV2的检测[J].动物医学进展,2004,25(1)：74-76
[52]Opriessnig, T, Janke, B HHalbur, P G. Cardiovascular lesions in pigs naturally or experimentally infected with porcine circovirus type 2[J]. J Comp Pathol,2006,134(1):105-110
[53]Yu, S, Opriessnig, T, Kitikoon, P, Nilubol, D, Halbur, P GThacker, E. Porcine circovirus type 2 (PCV2) distribution and replication in tissues and immune cells in early infected pigs[J]. Vet Immunol Immunopathol,2007,115(3-4):261-272
[54]云涛,倪征,刘光清,陈锦清.断奶仔猪多系统衰竭综合症发病机理之研究进展[J].中国农学通报,2005,21(11)：19-24
[55]Steiner, E, Balmelli, C, Herrmann, B, Summerfield, AMccullough, K. Porcine circovirus type 2 displays pluripotency in cell targeting[J]. Virology,2008,378(2):311-322
[56]Gilpin, D F, Mccullough, K, Meehan, B M, Mcneilly, F, Mcnair, I, Stevenson, L S, Foster, J C, Ellis, J A, Krakowka, S, Adair, B MAllan, G M. In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system[J]. Vet Immunol Immunopathol, 2003,94(3-4):149-161
[57]Finsterbusch, TMankertz, A. Porcine circoviruses--small but powerful[J]. Virus Res,2009,143(2): 177-183
[58]Jensen, T K, Boesen, H T, Vigre, HBoye, M. Detection of Lawsonia intracellularis in formalin-fixed porcine intestinal tissue samples:comparison of immunofluorescence and in-situ hybridization, and evaluation of the effects of controlled autolysis[J]. J Comp Pathol,2010,142(1): 1-8
[59]Rodriguez-Carino, C, Sanchez-Chardi, ASegales, J. Subcellular immunolocalization of porcine circovirus type 2 (PCV2) in lymph nodes from pigs with post-weaning multisystemic wasting syndrome (PMWS)[J]. J Comp Pathol,2010,142(4):291-299
[60]Yu, S, Halbur, P GThacker, E. Effect of porcine circovirus type 2 infection and replication on activated porcine peripheral blood mononuclear cells in vitro[J]. Vet Immunol Immunopathol,2009, 127(3-4):350-356
[61]Turner, M J, Medley, G F, Woodbine, K A, Slevin, J AGreen, L E. The relationship between porcine circovirus 2 antigen score and antibody titre and histology of lymph nodes in 375 euthanased sick and healthy pigs from 113 British pig farms with and without postweaning multisystemic wasting syndrome[J]. Prev Vet Med,2009,88(3):213-219
[62]Krakowka, S, Ellis, J A, Mcneilly, F, Ringler, S, Rings, D MAllan, G. Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2)[J]. Vet Pathol,2001,38(1):31-42
[63]Ladekjaer-Mikkelsen, a S, Nielsen, J, Stadejek, T, Storgaard, T, Krakowka, S, Ellis, J, Mcneilly, F, Allan, GBotner, A. Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2)[J]. Vet Microbiol,2002,89(2-3):97-114
[64]王先炜,姜平,韦显凯,李广明,李军星,董信田,蒋文明.免疫刺激商品断奶仔猪复制多系统衰竭综合征(PMWS)[J]畜牧兽医学报,2008,39(1)：66-71
[65]Kawashima, K, Tsunemitsu, H, Horino, R, Katsuda, K, Onodera, T, Shoji, T, Kubo, M, Haritani, MMurakami, Y. Effects of dexamethasone on the pathogenesis of porcine circovirus type 2 infection in piglets[J]. J Comp Pathol,2003,129(4):294-302
[66]Lefebvre, D J, Meerts, P, Costers, S, Misinzo, G, Barbe, F, Van Reeth, KNauwynck, H J. Increased porcine circovirus type 2 replication in porcine leukocytes in vitro and in vivo by concanavalin A stimulation[J]. Vet Microbiol,2008,132(1-2):74-86
[67]Lin, C M, Jeng, C R, Chang, H W, Guo, I C, Huang, Y L, Tsai, Y C, Chia, M YPang, V F. Characterization of porcine circovirus type 2 (PCV2) infection in swine lymphocytes using mitogen-stimulated peripheral blood lymphocytes from healthy PCV2-carrier pigs[J]. Vet Immunol Immunopathol,2008,124(3-4):355-366
[68]Ha, Y, Lee, Y H, Ahn, K K, Kim, BChae, C. Reproduction of postweaning multisystemic wasting syndrome in pigs by prenatal porcine circovirus 2 infection and postnatal porcine parvovirus infection or immunostimulation[J]. Vet Pathol,2008,45(6):842-848
[69]Shi, K, Li, H, Guo, X, Ge, X, Jia, H, Zheng, SYang, H. Changes in peripheral blood leukocyte subpopulations in piglets co-infected experimentally with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2[J]. Vet Microbiol,2008,129(3-4):367-377
[70]任彬.猪Ⅱ型圆环病毒感染的发病机理和仔猪断奶后多系统衰竭综合征[J].保健,2008,28(3)：2-4
[71]Kyriakis, S C, Saoulidis, K, Lekkas, S, Miliotis Ch, C, Papoutsis, P AKennedy, S. The effects of immuno-modulation on the clinical and pathological expression of postweaning multisystemic wasting syndrome[J]. J Comp Pathol,2002,126(1):38-46
[72]施开创,杨汉春,郭鑫,李焕荣,盖新娜,陈艳红,查振林.猪生殖与呼吸综合征病毒和猪圆环病毒2型共感染对猪外周血天然免疫细胞含量的影响[J].中国兽医科学,2007,37(01)：7-11
[73]司兴奎,郭鑫,杨汉春.猪圆环病毒2型感染对猪外周血单核细胞亚群含量的影响[J].中国预防兽医学报,2008,30(12)：973-977
[74]Segales, J, Alonso, F, Rosell, C, Pastor, J, Chianini, F, Campos, E, Lopez-Fuertes, L, Quintana, J, Rodriguez-Arrioja, G, Calsamiglia, M, Pujols, J, Dominguez, JDomingo, M. Changes in peripheral blood leukocyte populations in pigs with natural postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2001,81(1-2):37-44
[75]Darwich, L, Segales, J, Domingo, MMateu, E. Changes in CD4(+), CD8(+), CD4(+) CD8(+), and immunoglobulin M-positive peripheral blood mononuclear cells of postweaning multisystemic wasting syndrome-affected pigs and age-matched uninfected wasted and healthy pigs correlate with lesions and porcine circovirus type 2 load in lymphoid tissues[J]. Clin Diagn Lab Immunol,2002, 9(2):236-242
[76]Darwich, L, Segales, JMateu, E. Pathogenesis of postweaning multisystemic wasting syndrome caused by Porcine circovirus 2:An immune riddle[J]. Arch Virol,2004,149(5):857-874
[77]Nielsen, J, Vincent, I E, Botner, A, Ladekaer-Mikkelsen, a S, Allan, G, Summerfield, AMccullough, K C. Association of lymphopenia with porcine circovirus type 2 induced postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2003, 92(3-4):97-111
[78]聂立欣,罗满林,孔小明,于博.猪圆环病毒感染后部分免疫器官的组织化学检测[J].动物医学进展,2006,27(1)：58-61
[79]Sarli, G, Mandrioli, L, Laurenti, M, Sidoli, L, Cerati, C, Rolla, GMarcato, P S. Immunohistochemical characterisation of the lymph node reaction in pig post-weaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2001,83(1-2):53-67
[80]王天户,娄忠子,刘思当.猪PRRSV单独感染及与PCV2混合感染的免疫病理学研究[J].西南农业学报,2008,21(1)：187-190
[81]韩惠利,张书霞,施旅娟.PCV2对体外培养仔猪淋巴细胞凋亡的影响[J].南京农业大学学报,2008,31(1)：92-95
[82]Liu, J, Chen, IKwang, J. Characterization of a previously unidentified viral protein in porcine circovirus type 2-infected cells and its role in virus-induced apoptosis[J]. J Virol,2005,79(13): 8262-8274
[83]Chang, H W, Jeng, C R, Lin, C M, Liu, J J, Chang, C C, Tsai, Y C, Chia, M YPang, V F. The involvement of Fas/FasL interaction in porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus co-inoculation-associated lymphocyte apoptosis in vitro [J]. Vet Microbiol,2007,122(1-2):72-82
[84]华利忠,陈耿,张书霞.巨噬细胞介导PCV2诱导体外培养仔猪淋巴细胞凋亡的研究[J].南京农业大学学报,2010,33(3)：94-98
[85]Kiupel, M, Stevenson, G W, Galbreath, E J, North, A, Hogenesch, HMittal, S K. Porcine circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice[J]. BMC Vet Res,2005,1:7
[86]Shibahara, T, Sato, K, Ishikawa, YKadota, K. Porcine circovirus induces B lymphocyte depletion in pigs with wasting disease syndrome[J]. J Vet Med Sci,2000,62(11):1125-1131
[87]施旅娟,韩惠利,张书霞.PCV-2感染仔猪淋巴结中的病毒定位与细胞凋亡[J].中国农业科学,2008,41(1)：237-242
[88]Resendes, a R, Majo, N, Segales, J, Mateu, E, Calsamiglia, MDomingo, M. Apoptosis in lymphoid organs of pigs naturally infected by porcine circovirus type 2[J]. J Gen Virol,2004,85(Pt 10):2837-2844
[89]Liu, J, Chen, I, Du, Q, Chua, HKwang, J. The ORF3 protein of porcine circovirus type 2 is involved in viral pathogenesis in vivo[J]. J Virol,2006,80(10):5065-5073
[90]Sanchez, R E, Jr., Meerts, P, Nauwynck, H J, Ellis, J APensaert, M B. Characteristics of porcine circovirus-2 replication in lymphoid organs of pigs inoculated in late gestation or postnatally and possible relation to clinical and pathological outcome of infection[J]. J Vet Diagn Invest,2004, 16(3):175-185
[91]陈耿,华利忠,张书霞.猪圆环病毒2型对体外培养仔猪淋巴细胞转化能力及其活性的影响[J].中国兽医科学,2009,39(12)：1051-1056
[92]Vincent, IE, Carrasco, C P, Herrmann, B, Meehan, B M, Allan, G M, Summerfield, AMccullough, K C. Dendritic cells harbor infectious porcine circovirus type 2 in the absence of apparent cell modulation or replication of the virus[J]. J Virol,2003,77(24):13288-13300
[93]高文伟.猪圆环病毒的致病机理[J].南方养猪,2006,(205)：16-18
[94]王振生,聂晓华,李焕荣,孙英健,隋丽华,崔德凤.猪圆环病毒2型感染猪皮肤源树突状细胞炎性反应能力的变化[J].畜牧兽医学报,2009,40(12)：1776-1781
[95]周双海,赵东升,杨汉春,郭鑫,司兴奎.猪圆环病毒2型感染不会诱发猪肺泡巨噬细胞凋亡[J].北京农学院学报,2006,21(4)：37-39
[96]周双海,赵东升,郭鑫,杨汉春.PCV2感染对猪肺泡巨噬细胞受体数量和吞噬功能的影响[J].北京农学院学报,2006,21(1)：21-23
[97]周双海,赵东升,磨美兰,郭鑫,杨汉春.猪圆环病毒2型感染对猪肺泡巨噬细胞生物学活性的影响[J].中国兽医科技,2005,35(10)：775-778
[98]Chang, H W, Jeng, C R, Lin, T L, Liu, J J, Chiou, M T, Tsai, Y C, Chia, M Y, Jan, T RPang, V F. Immunopathological effects of porcine circovirus type 2 (PCV2) on swine alveolar macrophages by in vitro inoculation[J]. Vet Immunol Immunopathol,2006,110(3-4):207-219
[99]West, K H, Bystrom, J M, Wojnarowicz, C, Shantz, N, Jacobson, M, Allan, G M, Haines, D M, Clark, E G, Krakowka, S, Mcneilly, F, Konoby, C, Martin, KEllis, J A. Myocarditis and abortion associated with intrauterine infection of sows with porcine circovirus 2[J]. J Vet Diagn Invest,1999, 11(6):530-532
[100]陈耿,赵焱,包银莉,孟玲玲,田忠园,李桂平,华利忠,张书霞.PCV2对体外培养仔猪脾细胞分泌细胞因子的动态影响[J].兽医科技,2009,41(9)：58-60
[101]司兴奎,郭鑫,杨汉春.猪圆环病毒2型感染后猪外周血淋巴细胞IL-2、IL-4、IL-10、 IL-12p40、IFN-γ和TNF-a mRNA转录的变化[J].畜牧兽医学报,2009,40(1)：78-82
[102]Sipos, W, Duvigneau, J C, Willheim, M, Schilcher, F, Hartl, R T, Hofbauer, G, Exel, B, Pietschmann, PSchmoll, F. Systemic cytokine profile in feeder pigs suffering from natural postweaning multisystemic wasting syndrome (PMWS) as determined by semiquantitative RT-PCR and flow cytometric intracellular cytokine detection[J]. Vet Immunol Immunopathol,2004,99(1-2): 63-71
[103]Shi, K C, Guo, X, Ge, X N, Liu, QYang, H C. Cytokine mRNA expression profiles in peripheral blood mononuclear cells from piglets experimentally co-infected with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2[J]. Vet Microbiol,2009,
[104]Kim, JChae, C. Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 in porcine circovirus 2-induced granulomatous inflammation[J]. J Comp Pathol,2004,131(2-3):121-126
[105]周双海,杨汉春,郭鑫,陈艳红,查振林.猪圆环病毒2型感染对猪CD80和CD86 mRNA表达的影响[J].中国兽医学报,2007,27(2)：159-167
[106]周双海,杨汉春,郭鑫,司兴奎,赵东升.PCV2感染对猪MCP-1和IL-8 mRNA表达的影响[J].中国兽医科学,2006,36(06)：468-471
[107]张宏彪,韩惠利,刘世超,陈荣荣,李浩扬,张书霞.猪圆环病毒2型对体外培养的仔猪淋巴细胞抗氧化能力的影响[J].畜牧与兽医,2008,40(6)：9-12
[108]Kerr, J F, Wyllie, a HCurrie, a R. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J]. Br J Cancer,1972,26(4):239-257
[109]李超,伏圣博,刘华玲,马欣荣.细胞凋亡研究进展[J].世界科技研究与发展,2007,29(3)：45-53
[110]王忠田,陈光华,程永生.病毒感染和细胞的凋亡[J].畜牧兽医科技信息,2004,11：10-11
[111]Johnstone, R W, Ruefli, a ALowe, S W. Apoptosis:a link between cancer genetics and chemotherapy[J]. Cell,2002,108(2):153-164
[112]孙海丽,郭华,刘玉和,李挺,肖水芳.喉癌中Fas、FasL和Fas相关死亡结构域蛋白的表达及其意义[J].中国耳鼻咽喉头颈外科,2010,17(7)：343-345
[113]焦俊霞,高维娟.细胞凋亡的信号转导机制研究进展[J].中国老年学杂志,2010,30(6)：853-856
[114]Leblanc, A C. Natural cellular inhibitors of caspases[J]. Prog Neuropsychopharmacol Biol Psychiatry,2003,27(2):215-229
[115]陈本阳,张智博,唐璇,彭旭.大鼠脑缺血再灌注后神经细胞凋亡及Fas凋亡通路相关因子表达及意义[J].中国现在医学杂志,2009,19(1)：64-71
[116]Scott, F L, Stec, B, Pop, C, Dobaczewska, M K, Lee, J J, Monosov, E, Robinson, H, Salvesen, G S, Schwarzenbacher, RRiedl, S J. The Fas-FADD death domain complex structure unravels signalling by receptor clustering[J].Nature,2009,457(7232):1019-1022
[117]Matiba, B, Mariani, S MKrammer, P H. The CD95 system and the death of a lymphocyte[J]. Semin Immunol,1997,9(1):59-68
[118]徐丽丽,高世勇,季宇彬.细胞凋亡相关蛋白的研究进展[J].齐齐哈尔医学院学报,2008,29(11)：1361-1363
[119]卜兴江.细胞凋亡研究进展[J].生物学教学,2006,31(12)：7-9
[120]胡硕,胡成平.线粒体与细胞凋亡的研究进展[J].国际呼吸杂志,2006,26(6)：463-466
[121]Martinou, J C, Desagher, SAntonsson, B. Cytochrome c release from mitochondria:all or nothing[J]. Nat Cell Biol,2000,2(3):E41-43
[122]Norberg, E, Orrenius, SZhivotovsky, B. Mitochondrial regulation of cell death:processing of apoptosis-inducing factor (AIF)[J]. Biochem Biophys Res Commun,2010,396(1):95-100
[123]王瑞娟,彭瑞云,高亚兵,徐新萍,常公民,马俊杰,李杨,王水明AIF、Bax和Bcl-2在中子及γ射线照射致肠道损伤中的表达[J].解放军医学杂志,2009,34(11)：1356-1361
[124]Momoi, T. Caspases involved in ER stress-mediated cell death[J]. J Chem Neuroanat,2004, 28(1-2):101-105
[125]Nakagawa, T, Zhu, H, Morishima, N, Li, E, Xu, J, Yankner, B AYuan, J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta[J]. Nature,2000, 403(6765):98-103
[126]张小霞,张忠信.病毒对细胞凋亡的影响及作用机理[J].中国病毒学,2002,17(3)：289-295
[127]王春艳.病毒感染与细胞凋亡[J].细胞与分子免疫学杂志,2007,23(4)：387-389
[128]Roulston, A, Marcellus, R CBranton, P E. Viruses and apoptosis[J]. Annu Rev Microbiol,1999, 53:577-628
[129]Muller, ARudel, T. Modification of host cell apoptosis by viral and bacterial pathogens [J]. Int J Med Microbiol,2001,291(3):197-207
[130]Ezoe, H, Fatt, R BMak, S. Degradation of intracellular DNA in KB cells infected with cyt mutants of human adenovirus type 12[J]. J Virol,1981,40(1):20-27
[131]曲鸿飞,李慧姣.鸡传染性贫血病毒研究进展[J].中国兽药杂志,2010,44(3)：52-56
[132]刘玉锋,佘锐萍,李慧姣,靳红,梁明珍,刘玉如,寸钢彪IBDV超强毒株感染SPF鸡后法氏囊淋巴细胞凋亡及Bax和Bcl-2蛋白动态表达的研究[J].中国农业科学,2005,38(2)：405-409
[133]赵晓平.细胞凋亡研究进展[J].阴山学刊,2006,20(2)：33-35
[134]Nichols, J E, Niles, J ARoberts, N J, Jr. Human lymphocyte apoptosis after exposure to influenza A virus[J]. J Virol,2001,75(13):5921-5929
[135]刘小方,邹声泉.丙肝病毒感染与细胞凋亡[J].国外医学外科学分册,2001,28(4)：193-194
[136]王艾琳,李坚.病毒与细胞凋亡[J].自然杂志,2004,26(3)：125-128
[137]郭爱珍,陆承平.病毒感染调控细胞凋亡[J].中国兽医杂志,1998,24(7)：46-47
[138]代文君,王洪梅,杨少华,宋玲玲,高东,杨宏军,王立群,仲跻峰,何洪彬.小RNA病毒与细胞凋亡[J].家畜生态学报,2010,31(2)：109-112
[139]Wyllie, a H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation[J]. Nature,1980,284(5756):555-556
[140]肖东杰,申红.淋巴细胞凋亡的研究进展[J].中国肿瘤生物治疗杂志,1997,4(3)：182
[141]Turpin, E, Luke, K, Jones, J, Tumpey, T, Konan, KSchultz-Cherry, S. Influenza virus infection increases p53 activity:role of p53 in cell death and viral replication[J]. J Virol,2005,79(14): 8802-8811
[142]Schultz-Cherry, SHinshaw, V S. Influenza virus neuraminidase activates latent transforming growth factor beta[J]. J Virol,1996,70(12):8624-8629
[143]Ishikawa, E, Nakazawa, M, Yoshinari, MMinami, M. Role of tumor necrosis factor-related apoptosis-inducing ligand in immune response to influenza virus infection in mice[J]. J Virol,2005, 79(12):7658-7663
[144]Finkel, T H, Tudor-Williams, G, Banda, N K, Cotton, M F, Curiel, T, Monks, C, Baba, T W, Ruprecht, R MKupfer, A. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV-and SIV-infected lymph nodes[J]. Nat Med,1995,1(2):129-134
[145]Wang, J, Guan, E, Roderiquez, GNorcross, M A. Synergistic induction of apoptosis in primary CD4(+) T cells by macrophage-tropic HIV-1 and TGF-betal[J]. J Immunol,2001,167(6): 3360-3366
[146]Westendorp, M O, Frank, R, Ochsenbauer, C, Stricker, K, Dhein, J, Walczak, H, Debatin, K MKrammer, P H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gpl20[J]. Nature,1995,375(6531):497-500
[147]Kim, N, Dabrowska, A, Jenner, R GAldovini, A. Human and simian immunodeficiency virus-mediated upregulation of the apoptotic factor TRAIL occurs in antigen-presenting cells from AIDS-susceptible but not from AIDS-resistant species[J]. J Virol,2007,81(14):7584-7597
[148]Gulow, K, Kaminski, M, Darvas, K, Suss, D, Li-Weber, MKrammer, P H. HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death[J].J Immunol, 2005,174(9):5249-5260
[149]马晓丽,毛炳宇,赵晖,张燕,张红卫.传染性法氏囊病病毒感染对鸡脾脏B淋巴细胞的影响[J].山东农业科学,1998,(1)：17-18
[150]曹永长,毕英佐,罗晚秋,何洁.传染性囊病病毒诱导细胞凋亡的初步观察[J].中国兽医杂 志,1997,23(3)：5-7
[151]Tham, K MMoon, C D. Apoptosis in cell cultures induced by infectious bursal disease virus following in vitro infection[J]. Avian Dis,1996,40(1):109-113
[152]Summerfield, A, Zingle, K, Inumaru, SMccullough, K C. Induction of apoptosis in bone marrow neutrophil-lineage cells by classical swine fever virus[J]. J Gen Virol,2001,82(Pt 6):1309-1318
[153]Gomez-Villamandos, J C, Salguero, F J, Ruiz-Villamor, E, Sanchez-Cordon, P J, Bautista, M JSierra, M A. Classical Swine Fever:pathology of bone marrow[J]. Vet Pathol,2003,40(2): 157-163
[154]张云德,王建科,张强.猪瘟病毒引起免疫抑制的研究[J].湖北农业科学,2009,48(6)：1519-1522
[155]Bruschke, C J, Hulst, M M, Moormann, R J, Van Rijn, P AVan Oirschot, J T. Glycoprotein Erns of pestiviruses induces apoptosis in lymphocytes of several species[J]. J Virol,1997,71(9): 6692-6696
[156]Lopez-Soria, S, Segales, J, Rose, N, Vinas, M J, Blanchard, P, Madec, F, Jestin, A, Casal, JDomingo, M. An exploratory study on risk factors for postweaning multisystemic wasting syndrome (PMWS) in Spain[J]. Prev Vet Med,2005,69(1-2):97-107
[157]Rose, N, Larour, G, Le Diguerher, G, Eveno, E, Jolly, J P, Blanchard, P, Oger, A, Le Dimna, M, Jestin, AMadec, F. Risk factors for porcine post-weaning multisystemic wasting syndrome (PMWS) in 149 French farrow-to-finish herds[J]. Prev Vet Med,2003,61(3):209-225
[158]Yoshikawa, T, Saito, H, Osaki, T, Matsumoto, S, Tsujitani, SIkeguchi, M. Elevated Fas expression is related to increased apoptosis of circulating CD8+T cell in patients with gastric cancer[J]. J Surg Res,2008,148(2):143-151
[159]Carrington, P E, Sandu, C, Wei, Y, Hill, J M, Morisawa, G, Huang, T, Gavathiotis, EWerner, M H. The structure of FADD and its mode of interaction with procaspase-8[J]. Mol Cell,2006,22(5): 599-610
[160]Koh, W S, Yang, K HKaminski, N E. Cyclic AMP is an essential factor in immune responses[J]. Biochem Biophys Res Commun,1995,206(2):703-709
[161]洪伟彬,姜平,王先炜,李玉峰,唐波,王兴龙.猪圆环病毒2型SH毒株免疫原性[J].中国兽医学报,2009,29(8)：955-958
[162]夏少山.猪圆环病毒Ⅱ型分离鉴定及其ORF2基因在昆虫细胞中的表达和ELISA检测抗体方法的建立[D].扬州：扬州大学,2009：23-39.
[163]De Milito, A, Morch, C, Sonnerborg, AChiodi, F. Loss of memory (CD27) B lymphocytes in HIV-1 infection[J]. AIDS,2001,15(8):957-964
[164]Krammer, P H. CD95's deadly mission in the immune system[J]. Nature,2000,407(6805): 789-795
[165]贾山,任铁玲,张绪超,钟赛贤.镉对小鼠淋巴细胞增殖功能、IL-2影响与cAMP的关系[J].现在预防医学,2004,31(4)：487-492
[166]G, C E. Post2weaning multisystemic wasting syndrome[J]. Proceeding of t he American Association of Swine Practitioners,1997, (28):499-501
[167]张琦,李书华,王淑杰,蔡雪辉.猪圆环病毒感染诊断方法研究进展[J].动物医学进展,2008,29(6)：90-93
[168]Adachi, N, Hirota, M, Hamaguchi, M, Okamoto, K, Watanabe, KEndo, F. Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome[J]. Clin Chim Acta,2004,342(1-2):127-136
[169]Wang, X, Jiang, P, Li, Y, Jiang, WDong, X. Protection of pigs against post-weaning multisystemic wasting syndrome by a recombinant adenovirus expressing the capsid protein of porcine circovirus type 2[J]. Vet Microbiol,2007,121(3-4):215-224
[170]Harms, P A, Sorden, S D, Halbur, P G, Bolin, S R, Lager, K M, Morozov, IPaul, P S. Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus[J]. Vet Pathol,2001, 38(5):528-539
[171]Langohr, I M, Stevenson, G W, Nelson, E A, Lenz, S D, Hogenesch, H, Wei, HPogranichniy, R M. Vascular lesions in pigs experimentally infected with porcine circovirus type 2 serogroup B[J]. Vet Pathol,2010,47(1):140-147
[172]Resendes, a R, Majo, N, Van Den Ingh, T S, Mateu, E, Domingo, M, Calsamiglia, MSegales, J. Apoptosis in postweaning multisystemic wasting syndrome (PMWS) hepatitis in pigs naturally infected with porcine circovirus type 2 (PCV2)[J]. Vet J,2010,
[173]Rosell, C, Segales, JDomingo, M. Hepatitis and staging of hepatic damage in pigs naturally infected with porcine circovirus type 2[J]. Vet Pathol,2000,37(6):687-692
[174]Ben-Ari, Z, Schmilovotz-Weiss, H, Belinki, A, Pappo, O, Sulkes, J, Neuman, M G, Kaganovsky, E, Kfir, B, Tur-Kaspa, RKlein, T. Circulating soluble cytochrome c in liver disease as a marker of apoptosis[J]. J Intern Med,2003,254(2):168-175
[175]黄伶.血清细胞色素c测定对危重病患者预警作用的临床研究[D].济南：山东大学,2006：1-35.
[176]Barczyk, K, Kreuter, M, Pryjma, J, Booy, E P, Maddika, S, Ghavami, S, Berdel, W E, Roth, JLos, M. Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy[J]. Int J Cancer,2005,116(2):167-173
[177]Marie-Jose'Mhawej, Cecile Brunet-Franc-Ois, Raphaelfonteneau, Damienernst, Virginieferre, Guy-Bartstan, Francois RaffiH.Moog, C. Apoptosis characterizes immunological failure of HFV infected patients[J]. Control Engineering Practice,2009,17:798-804
[178]English, R V, Johnson, C M, Gebhard, D HTompkins, M B. In vivo lymphocyte tropism of feline immunodeficiency virus[J]. J Virol,1993,67(9):5175-5186
[179]Schat, K A. Chicken anemia virus[J]. Curr Top Microbiol Immunol,2009,331:151-183
[180]Li, X M, Qian, P, Shi, D S, Jin, M L, Lan, S YChen, H C. [Induction or inhibition of apoptosis by pseudorabies virus ea strain in suckling piglets][J]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai),2003,35(4):325-330
[181]Mandrioli, L, Sarli, G, Panarese, S, Baldoni, SMarcato, P S. Apoptosis and proliferative activity in lymph node reaction in postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2004,97(1-2):25-37
[182]李超,伏圣博,刘华玲,马欣荣.细胞凋亡研究进展[J].世界科技研究与发展,2007,29(3)：45-53
[183]周建华,丛国正,高闪电,常惠芸.细胞凋亡的研究进展[J].生物技术通讯,2008,19(2)：274-276
[184]Gupta, S. Molecular steps of death receptor and mitochondrial pathways of apoptosis [J]. Life Sci, 2001,69(25-26):2957-2964
[185]Gloire, G, Charlier, EPiette, J. Regulation of CD95/APO-1/Fas-induced apoptosis by protein phosphatases[J]. Biochem Pharmacol,2008,76(11):1451-1458
[186]Brenner, D, Krammer, P HArnold, R. Concepts of activated T cell death[J]. Crit Rev Oncol Hematol,2008,66(1):52-64
[187]史毓杰,江振友,孙晗笑.HIV诱导T细胞凋亡机制研究进展[J].中国皮肤性病学杂志,2005,19(3)：179-182
[188]Desagher, SMartinou, J C. Mitochondria as the central control point of apoptosis [J]. Trends Cell Biol,2000,10(9):369-377
[189]Livak, K JSchmittgen, T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods,2001,25(4):402-408
[190]李燕华,李瑶宣,李吕力,王铁建.脑缺血大鼠水通道蛋白29mRNA表达与钙离子浓度的改变及其关系[J].临床神经病学杂志,2008,21(2)：129-132
[191]Kirkin, V, Joos, SZornig, M. The role of Bcl-2 family members in tumorigenesis[J]. Biochim Biophys Acta,2004,1644(2-3):229-249
[192]Vogel, M W. Cell death, Bcl-2, Bax, and the cerebellum[J]. Cerebellum,2002,1(4):277-287
[193]Mcconkey, D JOrrenius, S. Signal transduction pathways in apoptosis[J]. Stem Cells,1996, 14(6):619-631
[194]Scaffidi, C, Fulda, S, Srinivasan, A, Friesen, C, Li, F, Tomaselli, K J, Debatin, K M, Krammer, P HPeter, M E. Two CD95 (APO-1/Fas) signaling pathways [J]. EMBO J,1998,17(6):1675-1687
[195]Fischer, B, Coelho, D, Dufour, P, Bergerat, J P, Denis, J M, Gueulette, JBischoff, P. Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53-dependent apoptosis[J]. Biochem Biophys Res Commun,2003,306(2):516-522
[196]Lee, W Y, Lim, D S, Ko, S H, Park, Y J, Ryu, K S, Ahn, M Y, Kim, Y R, Lee, D WCho, C W. Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells[J]. J Photochem Photobiol B,2004,75(3):119-126
[197]Zhang, H, Zhao, D, Wang, ZZheng, D. Diazoxide preconditioning alleviates caspase-dependent and caspase-independent apoptosis induced by anoxia-reoxygenation of PC12 cells[J]. J Biochem, 2010,
[198]Bao, QShi, Y. Apoptosome:a platform for the activation of initiator caspases[J]. Cell Death Differ,2007,14(1):56-65
[199]Hocsak, E, Racz, B, Szabo, A, Pozsgai, E, Szigeti, A, Szigeti, E, Gallyas, F, Jr., Sumegi, B, Javor, SBellyei, S. TIP47 confers resistance to taxol-induced cell death by preventing the nuclear translocation of AIF and Endonuclease G[J]. Eur J Cell Biol,2010,89(11):853-861
[200]王瑞娟,彭瑞云,高亚兵,徐新萍,常公民,马俊杰,李杨,王水明AIF、Bax和Bcl-2在中子及γ射线照射致肠道损伤中的表达[J].解放军医学杂志,2009,34(11)：1356-1359
[201]于翠娟,孟艳玲,王成济,杨安钢.凋亡诱导因子是线粒体内介导核凋亡的最主要蛋白质之[J].生物化学与生物物理进展,2002,29(2)：177-179
[202]Norberg, E, Orrenius, SZhivotovsky, B. Mitochondrial regulation of cell death:processing of apoptosis-inducing factor (AIF)[J]. Biochem Biophys Res Commun,396(1):95-100
[203]Green, D RReed, J C. Mitochondria and apoptosis[J]. Science,1998,281(5381):1309-1312
[204]Asher, E, Payne, C MBernstein, C. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy. II. Induction of non-classic apoptosis ("para-apoptosis") by tritiated thymidine[J]. Leuk Lymphoma,1995,19(1-2): 107-119
[205]French, L E, Hahne, M, Viard, I, Radlgruber, G, Zanone, R, Becker, K, Muller, CTschopp, J. Fas and Fas ligand in embryos and adult mice:ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover[J]. J Cell Biol,1996, 133(2):335-343
[206]Sproll, K C, Ballo, H, Hoffmann, T K, Scheckenbach, K, Koldovsky, U, Balz, V, Hafner, D, Ramp, UBier, H. Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human squamous cell carcinomas of the head and neck (SCCHN)?[J]. Oral Oncol,2009,45(1):69-84
[207]曾文军,王柳均,樊翌明,吴志华.二期梅毒患者外周血淋巴细胞凋亡及其Fas、FasL表达的研究[J].医学理论与实践,2008,21(6)：646-648
[208]Shrestha, BDiamond, M S. Fas ligand interactions contribute to CD8+T-cell-mediated control of West Nile virus infection in the central nervous system[J]. J Virol,2007,81(21):11749-11757
[209]Benhamla, T, Tirouche, Y D, Abaoub-Germain, ATheodore, F. [The onset of psychiatric disorders and Wilson's disease][J]. Encephale,2007,33(6):924-932
[210]李琪佳,王峰,付文娟,孙瑞军,白俊清,王志强.骨肉瘤组织FLIP和FADD及Caspase-8蛋白表达与细胞凋亡相关性的研究[J].中国肿瘤防治杂志,2009,16(22)：1797-1800
[211]Wong, B, Arron, JChoi, Y. T cell receptor signals enhance susceptibility to Fas-mediated apoptosis[J]. J Exp Med,1997,186(11):1939-1944
[212]Mizutani, Y, Yoshida, O, Ukimura, O, Kawauchi, A, Bonavida, BMiki, T. Prognostic significance of a combination of soluble Fas and soluble Fas ligand in the serum of patients with Ta bladder cancer[J]. Cancer Biother Radiopharm,2002,17(5):563-567
[213]关秀茹,刘晓民,高光强,崔丽娟,杜柏岩,辛晓敏.Fas系统介导的细胞凋亡与自身免疫性甲状腺疾病关系的研究[J].中华微生物学和免疫学杂志,2001,21(1)：74
[214]Blanco-Colio, L M, Martin-Ventura, J L, Tunon, J, Garcia-Camarero, T, Berrazueta, J REgido, J. Soluble Fas ligand plasma levels are associated with forearm reactive hyperemia in subjects with coronary artery disease:a novel biomarker of endothelial function?[J]. Atherosclerosis,2008, 201(2):407-412
[215]Dowd, D R, Ryerse, J S, Macdonald, P N, Miesfeld, R LKamradt, M C. Crosstalk during Ca2+-, cAMP-, and glucocorticoid-induced gene expression in lymphocytes [J]. Mol Cell Endocrinol,1997, 128(1-2):29-37
[216]Saitoh, M, Nagai, K, Yaguchi, T, Fujikawa, Y, Ikejiri, K, Yamamoto, S, Nakagawa, K, Yamamura, TNishizaki, T. Arachidonic acid peroxides induce apoptotic Neuro-2A cell death in association with intracellular Ca(2+) rise and mitochondrial damage independently of caspase-3 activation[J]. Brain Res,2003,991(1-2):187-194
[217]邓守恒,孙各琴,陈崇宏Ca2+、 cAMP、cGMP在硒化壳聚糖诱导的NB4细胞凋亡中的作用[J].陕西医学杂志,2007,36(4)：415-417
[218]Mcconkey, D JOrrenius, S. The role of calcium in the regulation of apoptosis[J]. Biochem Biophys Res Commun,1997,239(2):357-366
[219]Gordienko, D V, Harhun, M I, Kustov, M V, Pucovsky, VBolton, T B. Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+release induced by voltage-gated Ca2+entry[J]. Cell Calcium,2008,43(2): 122-141
[220]方以群,刘景昌,李斌,周时粉,张洪柱.高压氧对沙鼠脑缺血海马神经细胞Ca2+-ATP酶活力的影响[J].中华航海医学与高气压医学杂志,2006,13(3)：156-158
[221]王岚,吕家高,张存泰,程冕,刘念,阮燕菲,王琳.钙调蛋白激酶Ⅱ信号转导途径在血管紧张素Ⅱ致心肌肥大反应中的调控作用[J].华中科技大学学报(医学版),2009,38(1)：27-30
[222]张吉仲.藏药帕如热对实验动物脏腑cAMP、cGMP含量影响的实验研究[J].江西中医学院学报,2008,20(6)：56-57
[223]刘英学,赵长新,徐浩彦.精神分裂症患者血血浆和淋巴细胞中cAMP、cGMP水平[J].职业与健康,2006,26(12)：905-906
[224]叶华,郑学宝.半枝莲多糖对小鼠脾淋巴细胞cAMP含量的影响[J].广东医学院学报,2009,27(2)：124-125
[225]Su, Y, Huang, X, Raskovalova, T, Zacharia, L, Lokshin, A, Jackson, EGorelik, E. Cooperation of adenosine and prostaglandin E2 (PGE2) in amplification of cAMP-PKA signaling and immunosuppression[J]. Cancer Immunol Immunother,2008,57(11):1611-1623
[226]王丽蒋,宗勇,林映才,马现永,蒋守群.环腺苷酸(cAMP)及其抗病生物学作用[J].饲料工业,2009,30(7)：7-9
[227]Thomson, B J. Viruses and apoptosis[J]. Int J Exp Pathol,2001,82(2):65-76
[228]于学武.病毒感染诱导细胞凋亡分子机制的研究进展[J].现代畜牧兽医,2010,10(6)：79-82
[229]彭开松,佘锐萍.动物病毒与宿主细胞的细胞凋亡[J].中国兽医杂志,2004,40(11)：40-44
[230]Li, T, Qiu, Z, Zhang, L, Han, Y, He, W, Liu, Z, Ma, X, Fan, H, Lu, W, Xie, J, Wang, H, Deng, GWang, A. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome[J]. J Infect Dis,2004,189(4):648-651
[231]Zhou, Y HChen, Z. Is the immune system impaired in patients with severe acute respiratory syndrome?[J]. Clin Infect Dis,2004,38(6):921-922; author reply 922
[232]张庆玲,丁彦青,贺莉,王蔚,张进华,王慧君,蔡俊杰,耿舰,陆药丹,罗元龙SARS病变组织细胞凋亡检测及其意义[J].第一军医大学学报,2003,23(8)：770-773
[233]Jacotot, E, Krust, B, Callebaut, C, Laurent-Crawford, a G, Blanco, JHovanessian, a G. HIV-1 envelope glycoproteins-mediated apoptosis is regulated by CD4 dependent and independent mechanisms [J]. Apoptosis,1997,2(1):47-60
[234]陈耿,赵焱,包银莉,孟玲玲,田忠园,李桂平,华利忠,张书霞.PCV2对体外培养仔猪脾细胞分泌细胞因子的动态影响[J].兽医科技,2009,41(9)：58-60
[235]Reichmann, E. The biological role of the Fas/FasL system during tumor formation and progression[J]. Semin Cancer Biol,2002,12(4):309-315
[236]卢晓晔,钟雪云Caspases与细胞凋亡(综述)[J].暨南大学学报(医学版),2000,21(6)：121-124
[237]Shi, Y. Mechanisms of caspase activation and inhibition during apoptosis[J]. Mol Cell,2002, 9(3):459-470
[238]高旭辉.淋巴细胞钙通道及细胞内钙离子的研究进展[J].医学综述,2004,10(11)：641-643
[239]胡庭俊,梁纪兰,程富胜,陈吉祥张爱文.黄芪多糖对鸡脾脏淋巴细胞内游离钙离子浓度的影响[J].中兽医医药杂志,2001,(5)：4-6
[240]武建胜,董炳凤,廖圣宝.滋阴潜阳方对高血压大鼠淋巴细胞内PKA蛋白表达和cAMP水平的影响[J].安徽中医学院学报,2008,27(1)：46-48
[241]O'connell, P J, Wang, X, Leon-Ponte, M, Griffiths, C, Pingle, S CAhern, G P. A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells[J]. Blood,2006,107(3):1010-1017
[242]Roman, Y, Alfonso, A, Vieytes, M R, Ofuji, K, Satake, M, Yasumoto, TBotana, L M. Effects of Azaspiracids 2 and 3 on intracellular cAMP, [Ca2+], and pH[J]. Chem Res Toxicol,2004,17(10): 1338-1349
[243]Lipskaia, LLompre, a M. Alteration in temporal kinetics of Ca2+signaling and control of growth and proliferation[J]. Biol Cell,2004,96(1):55-68
[244]Gong, S L, Dong, L H, Liu, G W, Gong, P S, Lu, W T, Zhao, H G, Jia, X JZhao, Y. Effects of corticosterone, cAMP, cGMP, Ca2+, and protein kinase C on apoptosis of mouse thymocytes induced by X-ray irradiation[J]. Biomed Environ Sci,2008,21(2):167-172
[245]张秀娟,穆冲,岳金凤,季宇彬.从Ca2+通路研究紫草多糖促进小鼠淋巴细胞增殖的机制[J].中国现代药物应用,2007,1(24)：24-25
[246]郭国庆,沈伟哉.细胞凋亡调控的分子机制(综述)[J].暨南大学学报(医学版),2001,22(2)：20-23
[247]唐海林.钙离子信号与细胞凋亡关系的研究进展[J].南华大学学报医学版,2006,34(5)：663-666
[248]Jayaraman, T, Ondriasova, E, Ondrias, K, Harnick, D JMarks, a R. The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling[J]. Proc Natl Acad Sci USA, 1995,92(13):6007-6011
[249]Xie, C Y, Yang, W, Li, M, Ying, J, Tao, S J, Li, K, Dong, J HWang, X S. Cell apoptosis induced by delta-elemene in colorectal adenocarcinoma cells via a mitochondrial-mediated pathway[J]. Yakugaku Zasshi,2009,129(11):1403-1413
[250]Elrod, J W, Wong, R, Mishra, S, Vagnozzi, R J, Sakthievel, B, Goonasekera, S A, Karch, J, Gabel, S, Farber, J, Force, T, Brown, J H, Murphy, EMolkentin, J D. Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice[J]. J Clin Invest,2010,120(10):3680-3687
[251]Oh, S H, Lee, B HLim, S C. Cadmium induces apoptotic cell death in WI 38 cells via caspase-dependent Bid cleavage and calpain-mediated mitochondrial Bax cleavage by Bcl-2-independent pathway[J]. Biochem Pharmacol,2004,68(9):1845-1855
[252]王虎.Ca2+与内质网途径的细胞凋亡[J].国际病理科学与临床杂志,2006,26(4)：283-290
[253]Rizzuto, R, Pinton, P, Ferrari, D, Chami, M, Szabadkai, G, Magalhaes, P J, Di Virgilio, FPozzan, T. Calcium and apoptosis:facts and hypotheses[J]. Oncogene,2003,22(53):8619-8627
[254]Csordas, G, Renken, C, Varnai, P, Walter, L, Weaver, D, Buttle, K F, Balla, T, Mannella, C AHajnoczky, G. Structural and functional features and significance of the physical linkage between ER and mitochondria[J]. J Cell Biol,2006,174(7):915-921
[255]Sedlak, T WSnyder, S H. Messenger molecules and cell death:therapeutic implications [J]. JAMA,2006,295(1):81-89
[256]薛全福,王振纲.钙离子和细胞凋亡及药物调控[J].中国全科医学,2009,12(6B)：1126-1128
[257]Braun, a PSchulman, H. The multifunctional calcium/calmodulin-dependent protein kinase: from form to function[J]. Annu Rev Physiol,1995,57:417-445
[258]Yadav, M, Roach, S KSchorey, J S. Increased mitogen-activated protein kinase activity and TNF-alpha production associated with Mycobacterium smegmatis-but not Mycobacterium avium-infected macrophages requires prolonged stimulation of the calmodulin/calmodulin kinase and cyclic AMP/protein kinase A pathways[J]. J Immunol,2004,172(9):5588-5597
[259]于芳,张安民,李渊,胡淑萍.持续游泳训练对大鼠杏仁核cAMP浓度的影响[J].山西农业大学学报(自然科学版),2010,30(2)：105-107
[260]司维柯,李鹏,姚婕.苦参碱对HepG2细胞代谢水平和基因水平的影响[J].第三军医大学学报,2002,24(11)：1346-1349
[261]赵富清,张翠岚,彭兆云,谢宁,桂质丹,邓小琳.五参素对小鼠脾淋巴细胞内cAMP和cGMP含量的影响及细胞毒性作用[J].南京军医学院学报,2003,25(1)：4-6
[262]王丽,蒋宗勇,林映才,马现永,蒋守群.环腺苷酸(cAMP)及其抗病生物学作用[J].饲料工业,2009,30(7)：7-9
[263]Ma, W, Qi, Z, Smigel, A, Walker, R K, Verma, RBerkowitz, G A. Ca2+, cAMP, and transduction of non-self perception during plant immune responses[J]. Proc Natl Acad Sci USA,2009,106(49): 20995-21000
[264]蒋林,冯元璋,王琴,周兴挺,杨得坡.芦荟乙酰化甘露聚糖对肉仔鸡cAMP/cGMP与免疫功能的影响[J].中国畜牧杂志,2005,41(12)：7-11
[265]顾洛,陈晓红cAMP在急性胃粘膜损害中的作用的研究[J].中国应用生理学杂志,1994,10(1)：85-88
[266]唐胜球,董小英,邹晓庭.环腺苷酸的研究及其在动物营养中的应用[J].中国畜牧杂志,2006,42(5)：53-56
[2]Harding, J C. The clinical expression and emergence of porcine circovirus 2[J]. Vet Microbiol, 2004,98(2):131-135
[3]Chae, C. A review of porcine circovirus 2-associated syndromes and diseases[J]. Vet J,2005, 169(3):326-336
[4]蒋大良,余兴龙.猪圆环病毒2型致病机制研究进展[J].动物医学进展,2009,30(4)：94-98
[5]熊丕华,于雷.猪圆环病毒2型(PCV2)的致病机理[J].中国畜禽种业,2009,6：145-148
[6]Segales, J, Rosell, CDomingo, M. Pathological findings associated with naturally acquired porcine circovirus type 2 associated disease[J]. Vet Microbiol,2004,98(2):137-149
[7]史利军,任林柱,李刚.猪圆环病毒2型免疫抑制机理研究进展[J].动物医学进展,2009,30(3)：74-77
[8]Ellis, J A, Bratanich, A, Clark, E G, Allan, G, Meehan, B, Haines, D M, Harding, J, West, K H, Krakowka, S, Konoby, C, Hassard, L, Martin, KMcneilly, F. Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome[J]. J Vet Diagn Invest,2000,12(1):21-27
[9]Larochelle, R, Magar, RD'allaire, S. Comparative serologic and virologic study of commercial swine herds with and without postweaning multisystemic wasting syndrome[J]. Can J Vet Res, 2003,67(2):114-120
[10]Staebler, S, Sydler, T, Buergi, E, Mccullough, K, Mcneilly, F, Allan, GPospischil, A. PMWS:an emerging disease identified in archived porcine tissues[J]. Vet J,2005,170(1):132-134
[11]Chae, C. Postweaning multisystemic wasting syndrome:a review of aetiology, diagnosis and pathology[J]. Vet J,2004,168(1):41-49
[12]郎洪武,张广川,吴发权.猪断奶后多系统衰弱综合征的血清抗体检测[J].中国兽医科技,2000,30(3)：3-5
[13]赵东升,刘有昌,安福生,李祥健.近年来我国猪圆环病毒病的流行状况及分析[J].养猪,2009.1：57-59
[14]Ellis, J, Clark, E, Haines, D, West, K, Krakowka, S, Kennedy, SAllan, G M. Porcine circovirus-2 and concurrent infections in the field[J]. Vet Microbiol,2004,98(2):159-163
[15]Quintana, J, Segales, J, Rosell, C, Calsamiglia, M, Rodriguez-Arrioja, G M, Chianini, F, Folch, J M, Maldonado, J, Canal, M, Plana-Duran, JDomingo, M. Clinical and pathological observations on pigs with postweaning multisystemic wasting syndrome[J]. Vet Rec,2001,149(12):357-361
[16]赵浩军,王先炜,姜平,范伟兴,李晓成黄保续PMWS患病猪群中PCV2与CSFV、PPV, PRRSV混合感染的调查[J].畜牧与兽医,2007,39(3)：32-35
[17]Sanchez, R E, Jr., Meerts, P, Nauwynck, H JPensaert, M B. Change of porcine circovirus 2 target cells in pigs during development from fetal to early postnatal life[J]. Vet Microbiol,2003,95(1-2): 15-25
[18]邓云波,徐飞良,申玉仁.警惕专攻动物防御功能的病毒作祟[J].中国动物保健,2007,104：56-59
[19]Krakowka, S, Ellis, J, Mcneilly, F, Waldner, C, Rings, D MAllan, G. Mycoplasma hyopneumoniae bacterins and porcine circovirus type 2 (PCV2) infection:induction of postweaning multisystemic wasting syndrome (PMWS) in the gnotobiotic swine model of PCV2-associated disease[J]. Can Vet J,2007,48(7):716-724
[20]Lorincz, M, Csagola, A, Biksi, I, Szeredi, L, Dan, ATuboly, T. Detection of porcine circovirus in rodents-Short communication[J]. Acta Vet Hung,2010,58(2):265-268
[21]张骞.种猪场圆环病毒2型的血清学调查分析[J].疫情报告,2009,3(239)：60-61
[22]Allan, GM, Mcneilly, F, Cassidy, J P, Reilly, G A, Adair, B, Ellis, W AMcnulty, M S. Pathogenesis of porcine circovirus; experimental infections of colostrum deprived piglets and examination of pig foetal material[J]. Vet Microbiol,1995,44(1):49-64
[23]尹业师,黄伟坚,陈琼,刘海鹏,谢丽华,冯建远.猪圆环病毒感染的病理组织学和致病机理研究进展[J].动物医学进展,2006,27(11)：18-21
[24]Segales, J, Allan, G MDomingo, M. Porcine circovirus diseases[J]. Anim Health Res Rev,2005, 6(2):119-142
[25]Segales,J, Domingo, M, Chianini, F, Majo, N, Dominguez, J, Darwich, LMateu, E. Immunosuppression in postweaning multisystemic wasting syndrome affected pigs[J]. Vet Microbiol,2004,98(2):151-158
[26]Bolin, S R, Stoffregen, W C, Nayar, G PHamel, a L. Postweaning multisystemic wasting syndrome induced after experimental inoculation of cesarean-derived, colostrum-deprived piglets with type 2 porcine circovirus [J]. J Vet Diagn Invest,2001,13(3):185-194
[27]冷和平,温育铭,罗瑞国,邱江.生长猪散发性圆环病毒病的综合防治研究[J].养猪,2007,6：59-62
[28]韦英益,黄伟坚,尹业师,黄广顺,覃继顺.断奶仔猪多系统衰竭综合症的病理组织学观察[J].广西农业生物科学,2007,26：70-73
[29]王海花,李艳玲,汪德刚,张桂云.猪圆环病毒的研究进展[J].家畜生态学报,2006,27(4)： 110-112
[30]施兆红,王志远,刘洪波,韩惠利,施旅娟,张书霞.山东潍坊地区PMWS临床病例的病理学研究[J].畜牧与兽医,2007,39(5)：21-23
[31]冷和平.猪圆环病毒2型致病机理及防控措施研究的回顾和展望[J].猪业科学,2008,8：84-88
[32]Allan, G MEllis, J A. Porcine circoviruses:a review[J]. J Vet Diagn Invest,2000,12(1):3-14
[33]唐宁,吕艳丽,郭鑫,杨汉春,董军,司兴奎,王忠田.仔猪人工感染猪圆环病毒2型后的病理学特征[J].中国兽医杂志,2007,43(7)：19-20
[34]Wellenberg, G J, Stockhofe-Zurwieden, N, Boersma, W J, De Jong, M FElbers, a R. The presence of co-infections in pigs with clinical signs of PMWS in The Netherlands:a case-control study[J]. Res Vet Sci,2004,77(2):177-184
[35]Segales, JDomingo, M. Postweaning multisystemic wasting syndrome (PMWS) in pigs. A review[J]. Vet Q,2002,24(3):109-124
[36]Chianini, F, Majo, N, Segales, J, Dominguez, JDomingo, M. Immunohistochemical characterisation of PCV2 associate lesions in lymphoid and non-lymphoid tissues of pigs with natural postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol, 2003,94(1-2):63-75
[37]孙运.PCV2感染仔猪急性期蛋白的变化[D].南京：南京农业大学,2009：29-38.
[38]Sarli, G, Mandrioli, L, Panarese, S, Brunetti, B, Segales, J, Dominguez, JMarcato, P S. Characterization of interstitial nephritis in pigs with naturally occurring postweaning multisystemic wasting syndrome [J]. Vet Pathol,2008,45(1):12-18
[39]Seeliger, F A, Brugmann, M L, Kruger, L, Greiser-Wilke, I, Verspohl, J, Segales, JBaumgartner, W. Porcine circovirus type 2-associated cerebellar vasculitis in postweaning multisystemic wasting syndrome (PMWS)-affected pigs[J]. Vet Pathol,2007,44(5):621-634
[40]Darwich, L, Pie, S, Rovira, A, Segales, J, Domingo, M, Oswald, I PMateu, E. Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisystemic wasting syndrome[J]. J Gen Virol,2003,84(Pt 8):2117-2125
[41]Segales, J, Pastor, J, Cuenca, RDomingo, M. Haematological parameters in postweaning multisystemic wasting syndrome-affected pigs[J]. Vet Rec,2000,146(23):675-676
[42]Rosell, C, Segales, J, Plana-Duran, J, Balasch, M, Rodriguez-Arrioja, G M, Kennedy, S, Allan, G M, Mcneilly, F, Latimer, K SDomingo, M. Pathological, immunohistochemical, and in-situ hybridization studies of natural cases of postweaning multisystemic wasting syndrome (PMWS) in pigs[J]. J Comp Pathol,1999,120(1):59-78
[43]Calsamiglia, M, Segales, J, Quintana, J, Rosell, CDomingo, M. Detection of porcine circovirus types 1 and 2 in serum and tissue samples of pigs with and without postweaning multisystemic wasting syndrome[J]. J Clin Microbiol,2002,40(5):1848-1850
[44]王忠田,杨汉春.猪圆环病2型在PMWS患猪体内分布的初步研究[J].中国兽药杂志,2007,43(1)：23-25
[45]Mcintosh, K A, Tumber, A, Harding, J C, Krakowka, S, Ellis, J AHill, J E. Development and validation of a SYBR green real-time PCR for the quantification of porcine circovirus type 2 in serum, buffy coat, feces, and multiple tissues[J]. Vet Microbiol,2009,133(1-2):23-33
[46]Kennedy, S, Moffett, D, Mcneilly, F, Meehan, B, Ellis, J, Krakowka, SAllan, G M. Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus[J]. J Comp Pathol,2000, 122(1):9-24
[47]Park, J S, Ha, Y, Kwon, B, Cho, K D, Lee, B HChae, C. Detection of porcine circovirus 2 in mammary and other tissues from experimentally infected sows[J]. J Comp Pathol,2009,140(2-3): 208-211
[48]Mateusen, B, Maes, D G, Van Soom, A, Lefebvre, DNauwynck, H J. Effect of a porcine circovirus type 2 infection on embryos during early pregnancy[J]. Theriogenology,2007,68(6):896-901
[49]Opriessnig, T, Patterson, a R, Meng, X JHalbur, P G. Porcine circovirus type 2 in muscle and bone marrow is infectious and transmissible to naive pigs by oral consumption[J]. Vet Microbiol,2009, 133(1-2):54-64
[50]Segales, J, Calsamiglia, M, Olvera, A, Sibila, M, Badiella, LDomingo, M. Quantification of porcine circovirus type 2 (PCV2) DNA in serum and tonsillar, nasal, tracheo-bronchial, urinary and faecal swabs of pigs with and without postweaning multisystemic wasting syndrome (PMWS)[J], Vet Microbiol,2005,111(3-4):223-229
[51]梁红虎,罗满林,刘镇明.PCR对猪全血、血清、尿液和粪便中PCV2的检测[J].动物医学进展,2004,25(1)：74-76
[52]Opriessnig, T, Janke, B HHalbur, P G. Cardiovascular lesions in pigs naturally or experimentally infected with porcine circovirus type 2[J]. J Comp Pathol,2006,134(1):105-110
[53]Yu, S, Opriessnig, T, Kitikoon, P, Nilubol, D, Halbur, P GThacker, E. Porcine circovirus type 2 (PCV2) distribution and replication in tissues and immune cells in early infected pigs[J]. Vet Immunol Immunopathol,2007,115(3-4):261-272
[54]云涛,倪征,刘光清,陈锦清.断奶仔猪多系统衰竭综合症发病机理之研究进展[J].中国农学通报,2005,21(11)：19-24
[55]Steiner, E, Balmelli, C, Herrmann, B, Summerfield, AMccullough, K. Porcine circovirus type 2 displays pluripotency in cell targeting[J]. Virology,2008,378(2):311-322
[56]Gilpin, D F, Mccullough, K, Meehan, B M, Mcneilly, F, Mcnair, I, Stevenson, L S, Foster, J C, Ellis, J A, Krakowka, S, Adair, B MAllan, G M. In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system[J]. Vet Immunol Immunopathol, 2003,94(3-4):149-161
[57]Finsterbusch, TMankertz, A. Porcine circoviruses--small but powerful[J]. Virus Res,2009,143(2): 177-183
[58]Jensen, T K, Boesen, H T, Vigre, HBoye, M. Detection of Lawsonia intracellularis in formalin-fixed porcine intestinal tissue samples:comparison of immunofluorescence and in-situ hybridization, and evaluation of the effects of controlled autolysis[J]. J Comp Pathol,2010,142(1): 1-8
[59]Rodriguez-Carino, C, Sanchez-Chardi, ASegales, J. Subcellular immunolocalization of porcine circovirus type 2 (PCV2) in lymph nodes from pigs with post-weaning multisystemic wasting syndrome (PMWS)[J]. J Comp Pathol,2010,142(4):291-299
[60]Yu, S, Halbur, P GThacker, E. Effect of porcine circovirus type 2 infection and replication on activated porcine peripheral blood mononuclear cells in vitro[J]. Vet Immunol Immunopathol,2009, 127(3-4):350-356
[61]Turner, M J, Medley, G F, Woodbine, K A, Slevin, J AGreen, L E. The relationship between porcine circovirus 2 antigen score and antibody titre and histology of lymph nodes in 375 euthanased sick and healthy pigs from 113 British pig farms with and without postweaning multisystemic wasting syndrome[J]. Prev Vet Med,2009,88(3):213-219
[62]Krakowka, S, Ellis, J A, Mcneilly, F, Ringler, S, Rings, D MAllan, G. Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2)[J]. Vet Pathol,2001,38(1):31-42
[63]Ladekjaer-Mikkelsen, a S, Nielsen, J, Stadejek, T, Storgaard, T, Krakowka, S, Ellis, J, Mcneilly, F, Allan, GBotner, A. Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2)[J]. Vet Microbiol,2002,89(2-3):97-114
[64]王先炜,姜平,韦显凯,李广明,李军星,董信田,蒋文明.免疫刺激商品断奶仔猪复制多系统衰竭综合征(PMWS)[J]畜牧兽医学报,2008,39(1)：66-71
[65]Kawashima, K, Tsunemitsu, H, Horino, R, Katsuda, K, Onodera, T, Shoji, T, Kubo, M, Haritani, MMurakami, Y. Effects of dexamethasone on the pathogenesis of porcine circovirus type 2 infection in piglets[J]. J Comp Pathol,2003,129(4):294-302
[66]Lefebvre, D J, Meerts, P, Costers, S, Misinzo, G, Barbe, F, Van Reeth, KNauwynck, H J. Increased porcine circovirus type 2 replication in porcine leukocytes in vitro and in vivo by concanavalin A stimulation[J]. Vet Microbiol,2008,132(1-2):74-86
[67]Lin, C M, Jeng, C R, Chang, H W, Guo, I C, Huang, Y L, Tsai, Y C, Chia, M YPang, V F. Characterization of porcine circovirus type 2 (PCV2) infection in swine lymphocytes using mitogen-stimulated peripheral blood lymphocytes from healthy PCV2-carrier pigs[J]. Vet Immunol Immunopathol,2008,124(3-4):355-366
[68]Ha, Y, Lee, Y H, Ahn, K K, Kim, BChae, C. Reproduction of postweaning multisystemic wasting syndrome in pigs by prenatal porcine circovirus 2 infection and postnatal porcine parvovirus infection or immunostimulation[J]. Vet Pathol,2008,45(6):842-848
[69]Shi, K, Li, H, Guo, X, Ge, X, Jia, H, Zheng, SYang, H. Changes in peripheral blood leukocyte subpopulations in piglets co-infected experimentally with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2[J]. Vet Microbiol,2008,129(3-4):367-377
[70]任彬.猪Ⅱ型圆环病毒感染的发病机理和仔猪断奶后多系统衰竭综合征[J].保健,2008,28(3)：2-4
[71]Kyriakis, S C, Saoulidis, K, Lekkas, S, Miliotis Ch, C, Papoutsis, P AKennedy, S. The effects of immuno-modulation on the clinical and pathological expression of postweaning multisystemic wasting syndrome[J]. J Comp Pathol,2002,126(1):38-46
[72]施开创,杨汉春,郭鑫,李焕荣,盖新娜,陈艳红,查振林.猪生殖与呼吸综合征病毒和猪圆环病毒2型共感染对猪外周血天然免疫细胞含量的影响[J].中国兽医科学,2007,37(01)：7-11
[73]司兴奎,郭鑫,杨汉春.猪圆环病毒2型感染对猪外周血单核细胞亚群含量的影响[J].中国预防兽医学报,2008,30(12)：973-977
[74]Segales, J, Alonso, F, Rosell, C, Pastor, J, Chianini, F, Campos, E, Lopez-Fuertes, L, Quintana, J, Rodriguez-Arrioja, G, Calsamiglia, M, Pujols, J, Dominguez, JDomingo, M. Changes in peripheral blood leukocyte populations in pigs with natural postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2001,81(1-2):37-44
[75]Darwich, L, Segales, J, Domingo, MMateu, E. Changes in CD4(+), CD8(+), CD4(+) CD8(+), and immunoglobulin M-positive peripheral blood mononuclear cells of postweaning multisystemic wasting syndrome-affected pigs and age-matched uninfected wasted and healthy pigs correlate with lesions and porcine circovirus type 2 load in lymphoid tissues[J]. Clin Diagn Lab Immunol,2002, 9(2):236-242
[76]Darwich, L, Segales, JMateu, E. Pathogenesis of postweaning multisystemic wasting syndrome caused by Porcine circovirus 2:An immune riddle[J]. Arch Virol,2004,149(5):857-874
[77]Nielsen, J, Vincent, I E, Botner, A, Ladekaer-Mikkelsen, a S, Allan, G, Summerfield, AMccullough, K C. Association of lymphopenia with porcine circovirus type 2 induced postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2003, 92(3-4):97-111
[78]聂立欣,罗满林,孔小明,于博.猪圆环病毒感染后部分免疫器官的组织化学检测[J].动物医学进展,2006,27(1)：58-61
[79]Sarli, G, Mandrioli, L, Laurenti, M, Sidoli, L, Cerati, C, Rolla, GMarcato, P S. Immunohistochemical characterisation of the lymph node reaction in pig post-weaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2001,83(1-2):53-67
[80]王天户,娄忠子,刘思当.猪PRRSV单独感染及与PCV2混合感染的免疫病理学研究[J].西南农业学报,2008,21(1)：187-190
[81]韩惠利,张书霞,施旅娟.PCV2对体外培养仔猪淋巴细胞凋亡的影响[J].南京农业大学学报,2008,31(1)：92-95
[82]Liu, J, Chen, IKwang, J. Characterization of a previously unidentified viral protein in porcine circovirus type 2-infected cells and its role in virus-induced apoptosis[J]. J Virol,2005,79(13): 8262-8274
[83]Chang, H W, Jeng, C R, Lin, C M, Liu, J J, Chang, C C, Tsai, Y C, Chia, M YPang, V F. The involvement of Fas/FasL interaction in porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus co-inoculation-associated lymphocyte apoptosis in vitro [J]. Vet Microbiol,2007,122(1-2):72-82
[84]华利忠,陈耿,张书霞.巨噬细胞介导PCV2诱导体外培养仔猪淋巴细胞凋亡的研究[J].南京农业大学学报,2010,33(3)：94-98
[85]Kiupel, M, Stevenson, G W, Galbreath, E J, North, A, Hogenesch, HMittal, S K. Porcine circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice[J]. BMC Vet Res,2005,1:7
[86]Shibahara, T, Sato, K, Ishikawa, YKadota, K. Porcine circovirus induces B lymphocyte depletion in pigs with wasting disease syndrome[J]. J Vet Med Sci,2000,62(11):1125-1131
[87]施旅娟,韩惠利,张书霞.PCV-2感染仔猪淋巴结中的病毒定位与细胞凋亡[J].中国农业科学,2008,41(1)：237-242
[88]Resendes, a R, Majo, N, Segales, J, Mateu, E, Calsamiglia, MDomingo, M. Apoptosis in lymphoid organs of pigs naturally infected by porcine circovirus type 2[J]. J Gen Virol,2004,85(Pt 10):2837-2844
[89]Liu, J, Chen, I, Du, Q, Chua, HKwang, J. The ORF3 protein of porcine circovirus type 2 is involved in viral pathogenesis in vivo[J]. J Virol,2006,80(10):5065-5073
[90]Sanchez, R E, Jr., Meerts, P, Nauwynck, H J, Ellis, J APensaert, M B. Characteristics of porcine circovirus-2 replication in lymphoid organs of pigs inoculated in late gestation or postnatally and possible relation to clinical and pathological outcome of infection[J]. J Vet Diagn Invest,2004, 16(3):175-185
[91]陈耿,华利忠,张书霞.猪圆环病毒2型对体外培养仔猪淋巴细胞转化能力及其活性的影响[J].中国兽医科学,2009,39(12)：1051-1056
[92]Vincent, IE, Carrasco, C P, Herrmann, B, Meehan, B M, Allan, G M, Summerfield, AMccullough, K C. Dendritic cells harbor infectious porcine circovirus type 2 in the absence of apparent cell modulation or replication of the virus[J]. J Virol,2003,77(24):13288-13300
[93]高文伟.猪圆环病毒的致病机理[J].南方养猪,2006,(205)：16-18
[94]王振生,聂晓华,李焕荣,孙英健,隋丽华,崔德凤.猪圆环病毒2型感染猪皮肤源树突状细胞炎性反应能力的变化[J].畜牧兽医学报,2009,40(12)：1776-1781
[95]周双海,赵东升,杨汉春,郭鑫,司兴奎.猪圆环病毒2型感染不会诱发猪肺泡巨噬细胞凋亡[J].北京农学院学报,2006,21(4)：37-39
[96]周双海,赵东升,郭鑫,杨汉春.PCV2感染对猪肺泡巨噬细胞受体数量和吞噬功能的影响[J].北京农学院学报,2006,21(1)：21-23
[97]周双海,赵东升,磨美兰,郭鑫,杨汉春.猪圆环病毒2型感染对猪肺泡巨噬细胞生物学活性的影响[J].中国兽医科技,2005,35(10)：775-778
[98]Chang, H W, Jeng, C R, Lin, T L, Liu, J J, Chiou, M T, Tsai, Y C, Chia, M Y, Jan, T RPang, V F. Immunopathological effects of porcine circovirus type 2 (PCV2) on swine alveolar macrophages by in vitro inoculation[J]. Vet Immunol Immunopathol,2006,110(3-4):207-219
[99]West, K H, Bystrom, J M, Wojnarowicz, C, Shantz, N, Jacobson, M, Allan, G M, Haines, D M, Clark, E G, Krakowka, S, Mcneilly, F, Konoby, C, Martin, KEllis, J A. Myocarditis and abortion associated with intrauterine infection of sows with porcine circovirus 2[J]. J Vet Diagn Invest,1999, 11(6):530-532
[100]陈耿,赵焱,包银莉,孟玲玲,田忠园,李桂平,华利忠,张书霞.PCV2对体外培养仔猪脾细胞分泌细胞因子的动态影响[J].兽医科技,2009,41(9)：58-60
[101]司兴奎,郭鑫,杨汉春.猪圆环病毒2型感染后猪外周血淋巴细胞IL-2、IL-4、IL-10、 IL-12p40、IFN-γ和TNF-a mRNA转录的变化[J].畜牧兽医学报,2009,40(1)：78-82
[102]Sipos, W, Duvigneau, J C, Willheim, M, Schilcher, F, Hartl, R T, Hofbauer, G, Exel, B, Pietschmann, PSchmoll, F. Systemic cytokine profile in feeder pigs suffering from natural postweaning multisystemic wasting syndrome (PMWS) as determined by semiquantitative RT-PCR and flow cytometric intracellular cytokine detection[J]. Vet Immunol Immunopathol,2004,99(1-2): 63-71
[103]Shi, K C, Guo, X, Ge, X N, Liu, QYang, H C. Cytokine mRNA expression profiles in peripheral blood mononuclear cells from piglets experimentally co-infected with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2[J]. Vet Microbiol,2009,
[104]Kim, JChae, C. Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 in porcine circovirus 2-induced granulomatous inflammation[J]. J Comp Pathol,2004,131(2-3):121-126
[105]周双海,杨汉春,郭鑫,陈艳红,查振林.猪圆环病毒2型感染对猪CD80和CD86 mRNA表达的影响[J].中国兽医学报,2007,27(2)：159-167
[106]周双海,杨汉春,郭鑫,司兴奎,赵东升.PCV2感染对猪MCP-1和IL-8 mRNA表达的影响[J].中国兽医科学,2006,36(06)：468-471
[107]张宏彪,韩惠利,刘世超,陈荣荣,李浩扬,张书霞.猪圆环病毒2型对体外培养的仔猪淋巴细胞抗氧化能力的影响[J].畜牧与兽医,2008,40(6)：9-12
[108]Kerr, J F, Wyllie, a HCurrie, a R. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J]. Br J Cancer,1972,26(4):239-257
[109]李超,伏圣博,刘华玲,马欣荣.细胞凋亡研究进展[J].世界科技研究与发展,2007,29(3)：45-53
[110]王忠田,陈光华,程永生.病毒感染和细胞的凋亡[J].畜牧兽医科技信息,2004,11：10-11
[111]Johnstone, R W, Ruefli, a ALowe, S W. Apoptosis:a link between cancer genetics and chemotherapy[J]. Cell,2002,108(2):153-164
[112]孙海丽,郭华,刘玉和,李挺,肖水芳.喉癌中Fas、FasL和Fas相关死亡结构域蛋白的表达及其意义[J].中国耳鼻咽喉头颈外科,2010,17(7)：343-345
[113]焦俊霞,高维娟.细胞凋亡的信号转导机制研究进展[J].中国老年学杂志,2010,30(6)：853-856
[114]Leblanc, A C. Natural cellular inhibitors of caspases[J]. Prog Neuropsychopharmacol Biol Psychiatry,2003,27(2):215-229
[115]陈本阳,张智博,唐璇,彭旭.大鼠脑缺血再灌注后神经细胞凋亡及Fas凋亡通路相关因子表达及意义[J].中国现在医学杂志,2009,19(1)：64-71
[116]Scott, F L, Stec, B, Pop, C, Dobaczewska, M K, Lee, J J, Monosov, E, Robinson, H, Salvesen, G S, Schwarzenbacher, RRiedl, S J. The Fas-FADD death domain complex structure unravels signalling by receptor clustering[J].Nature,2009,457(7232):1019-1022
[117]Matiba, B, Mariani, S MKrammer, P H. The CD95 system and the death of a lymphocyte[J]. Semin Immunol,1997,9(1):59-68
[118]徐丽丽,高世勇,季宇彬.细胞凋亡相关蛋白的研究进展[J].齐齐哈尔医学院学报,2008,29(11)：1361-1363
[119]卜兴江.细胞凋亡研究进展[J].生物学教学,2006,31(12)：7-9
[120]胡硕,胡成平.线粒体与细胞凋亡的研究进展[J].国际呼吸杂志,2006,26(6)：463-466
[121]Martinou, J C, Desagher, SAntonsson, B. Cytochrome c release from mitochondria:all or nothing[J]. Nat Cell Biol,2000,2(3):E41-43
[122]Norberg, E, Orrenius, SZhivotovsky, B. Mitochondrial regulation of cell death:processing of apoptosis-inducing factor (AIF)[J]. Biochem Biophys Res Commun,2010,396(1):95-100
[123]王瑞娟,彭瑞云,高亚兵,徐新萍,常公民,马俊杰,李杨,王水明AIF、Bax和Bcl-2在中子及γ射线照射致肠道损伤中的表达[J].解放军医学杂志,2009,34(11)：1356-1361
[124]Momoi, T. Caspases involved in ER stress-mediated cell death[J]. J Chem Neuroanat,2004, 28(1-2):101-105
[125]Nakagawa, T, Zhu, H, Morishima, N, Li, E, Xu, J, Yankner, B AYuan, J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta[J]. Nature,2000, 403(6765):98-103
[126]张小霞,张忠信.病毒对细胞凋亡的影响及作用机理[J].中国病毒学,2002,17(3)：289-295
[127]王春艳.病毒感染与细胞凋亡[J].细胞与分子免疫学杂志,2007,23(4)：387-389
[128]Roulston, A, Marcellus, R CBranton, P E. Viruses and apoptosis[J]. Annu Rev Microbiol,1999, 53:577-628
[129]Muller, ARudel, T. Modification of host cell apoptosis by viral and bacterial pathogens [J]. Int J Med Microbiol,2001,291(3):197-207
[130]Ezoe, H, Fatt, R BMak, S. Degradation of intracellular DNA in KB cells infected with cyt mutants of human adenovirus type 12[J]. J Virol,1981,40(1):20-27
[131]曲鸿飞,李慧姣.鸡传染性贫血病毒研究进展[J].中国兽药杂志,2010,44(3)：52-56
[132]刘玉锋,佘锐萍,李慧姣,靳红,梁明珍,刘玉如,寸钢彪IBDV超强毒株感染SPF鸡后法氏囊淋巴细胞凋亡及Bax和Bcl-2蛋白动态表达的研究[J].中国农业科学,2005,38(2)：405-409
[133]赵晓平.细胞凋亡研究进展[J].阴山学刊,2006,20(2)：33-35
[134]Nichols, J E, Niles, J ARoberts, N J, Jr. Human lymphocyte apoptosis after exposure to influenza A virus[J]. J Virol,2001,75(13):5921-5929
[135]刘小方,邹声泉.丙肝病毒感染与细胞凋亡[J].国外医学外科学分册,2001,28(4)：193-194
[136]王艾琳,李坚.病毒与细胞凋亡[J].自然杂志,2004,26(3)：125-128
[137]郭爱珍,陆承平.病毒感染调控细胞凋亡[J].中国兽医杂志,1998,24(7)：46-47
[138]代文君,王洪梅,杨少华,宋玲玲,高东,杨宏军,王立群,仲跻峰,何洪彬.小RNA病毒与细胞凋亡[J].家畜生态学报,2010,31(2)：109-112
[139]Wyllie, a H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation[J]. Nature,1980,284(5756):555-556
[140]肖东杰,申红.淋巴细胞凋亡的研究进展[J].中国肿瘤生物治疗杂志,1997,4(3)：182
[141]Turpin, E, Luke, K, Jones, J, Tumpey, T, Konan, KSchultz-Cherry, S. Influenza virus infection increases p53 activity:role of p53 in cell death and viral replication[J]. J Virol,2005,79(14): 8802-8811
[142]Schultz-Cherry, SHinshaw, V S. Influenza virus neuraminidase activates latent transforming growth factor beta[J]. J Virol,1996,70(12):8624-8629
[143]Ishikawa, E, Nakazawa, M, Yoshinari, MMinami, M. Role of tumor necrosis factor-related apoptosis-inducing ligand in immune response to influenza virus infection in mice[J]. J Virol,2005, 79(12):7658-7663
[144]Finkel, T H, Tudor-Williams, G, Banda, N K, Cotton, M F, Curiel, T, Monks, C, Baba, T W, Ruprecht, R MKupfer, A. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV-and SIV-infected lymph nodes[J]. Nat Med,1995,1(2):129-134
[145]Wang, J, Guan, E, Roderiquez, GNorcross, M A. Synergistic induction of apoptosis in primary CD4(+) T cells by macrophage-tropic HIV-1 and TGF-betal[J]. J Immunol,2001,167(6): 3360-3366
[146]Westendorp, M O, Frank, R, Ochsenbauer, C, Stricker, K, Dhein, J, Walczak, H, Debatin, K MKrammer, P H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gpl20[J]. Nature,1995,375(6531):497-500
[147]Kim, N, Dabrowska, A, Jenner, R GAldovini, A. Human and simian immunodeficiency virus-mediated upregulation of the apoptotic factor TRAIL occurs in antigen-presenting cells from AIDS-susceptible but not from AIDS-resistant species[J]. J Virol,2007,81(14):7584-7597
[148]Gulow, K, Kaminski, M, Darvas, K, Suss, D, Li-Weber, MKrammer, P H. HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death[J].J Immunol, 2005,174(9):5249-5260
[149]马晓丽,毛炳宇,赵晖,张燕,张红卫.传染性法氏囊病病毒感染对鸡脾脏B淋巴细胞的影响[J].山东农业科学,1998,(1)：17-18
[150]曹永长,毕英佐,罗晚秋,何洁.传染性囊病病毒诱导细胞凋亡的初步观察[J].中国兽医杂 志,1997,23(3)：5-7
[151]Tham, K MMoon, C D. Apoptosis in cell cultures induced by infectious bursal disease virus following in vitro infection[J]. Avian Dis,1996,40(1):109-113
[152]Summerfield, A, Zingle, K, Inumaru, SMccullough, K C. Induction of apoptosis in bone marrow neutrophil-lineage cells by classical swine fever virus[J]. J Gen Virol,2001,82(Pt 6):1309-1318
[153]Gomez-Villamandos, J C, Salguero, F J, Ruiz-Villamor, E, Sanchez-Cordon, P J, Bautista, M JSierra, M A. Classical Swine Fever:pathology of bone marrow[J]. Vet Pathol,2003,40(2): 157-163
[154]张云德,王建科,张强.猪瘟病毒引起免疫抑制的研究[J].湖北农业科学,2009,48(6)：1519-1522
[155]Bruschke, C J, Hulst, M M, Moormann, R J, Van Rijn, P AVan Oirschot, J T. Glycoprotein Erns of pestiviruses induces apoptosis in lymphocytes of several species[J]. J Virol,1997,71(9): 6692-6696
[156]Lopez-Soria, S, Segales, J, Rose, N, Vinas, M J, Blanchard, P, Madec, F, Jestin, A, Casal, JDomingo, M. An exploratory study on risk factors for postweaning multisystemic wasting syndrome (PMWS) in Spain[J]. Prev Vet Med,2005,69(1-2):97-107
[157]Rose, N, Larour, G, Le Diguerher, G, Eveno, E, Jolly, J P, Blanchard, P, Oger, A, Le Dimna, M, Jestin, AMadec, F. Risk factors for porcine post-weaning multisystemic wasting syndrome (PMWS) in 149 French farrow-to-finish herds[J]. Prev Vet Med,2003,61(3):209-225
[158]Yoshikawa, T, Saito, H, Osaki, T, Matsumoto, S, Tsujitani, SIkeguchi, M. Elevated Fas expression is related to increased apoptosis of circulating CD8+T cell in patients with gastric cancer[J]. J Surg Res,2008,148(2):143-151
[159]Carrington, P E, Sandu, C, Wei, Y, Hill, J M, Morisawa, G, Huang, T, Gavathiotis, EWerner, M H. The structure of FADD and its mode of interaction with procaspase-8[J]. Mol Cell,2006,22(5): 599-610
[160]Koh, W S, Yang, K HKaminski, N E. Cyclic AMP is an essential factor in immune responses[J]. Biochem Biophys Res Commun,1995,206(2):703-709
[161]洪伟彬,姜平,王先炜,李玉峰,唐波,王兴龙.猪圆环病毒2型SH毒株免疫原性[J].中国兽医学报,2009,29(8)：955-958
[162]夏少山.猪圆环病毒Ⅱ型分离鉴定及其ORF2基因在昆虫细胞中的表达和ELISA检测抗体方法的建立[D].扬州：扬州大学,2009：23-39.
[163]De Milito, A, Morch, C, Sonnerborg, AChiodi, F. Loss of memory (CD27) B lymphocytes in HIV-1 infection[J]. AIDS,2001,15(8):957-964
[164]Krammer, P H. CD95's deadly mission in the immune system[J]. Nature,2000,407(6805): 789-795
[165]贾山,任铁玲,张绪超,钟赛贤.镉对小鼠淋巴细胞增殖功能、IL-2影响与cAMP的关系[J].现在预防医学,2004,31(4)：487-492
[166]G, C E. Post2weaning multisystemic wasting syndrome[J]. Proceeding of t he American Association of Swine Practitioners,1997, (28):499-501
[167]张琦,李书华,王淑杰,蔡雪辉.猪圆环病毒感染诊断方法研究进展[J].动物医学进展,2008,29(6)：90-93
[168]Adachi, N, Hirota, M, Hamaguchi, M, Okamoto, K, Watanabe, KEndo, F. Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome[J]. Clin Chim Acta,2004,342(1-2):127-136
[169]Wang, X, Jiang, P, Li, Y, Jiang, WDong, X. Protection of pigs against post-weaning multisystemic wasting syndrome by a recombinant adenovirus expressing the capsid protein of porcine circovirus type 2[J]. Vet Microbiol,2007,121(3-4):215-224
[170]Harms, P A, Sorden, S D, Halbur, P G, Bolin, S R, Lager, K M, Morozov, IPaul, P S. Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus[J]. Vet Pathol,2001, 38(5):528-539
[171]Langohr, I M, Stevenson, G W, Nelson, E A, Lenz, S D, Hogenesch, H, Wei, HPogranichniy, R M. Vascular lesions in pigs experimentally infected with porcine circovirus type 2 serogroup B[J]. Vet Pathol,2010,47(1):140-147
[172]Resendes, a R, Majo, N, Van Den Ingh, T S, Mateu, E, Domingo, M, Calsamiglia, MSegales, J. Apoptosis in postweaning multisystemic wasting syndrome (PMWS) hepatitis in pigs naturally infected with porcine circovirus type 2 (PCV2)[J]. Vet J,2010,
[173]Rosell, C, Segales, JDomingo, M. Hepatitis and staging of hepatic damage in pigs naturally infected with porcine circovirus type 2[J]. Vet Pathol,2000,37(6):687-692
[174]Ben-Ari, Z, Schmilovotz-Weiss, H, Belinki, A, Pappo, O, Sulkes, J, Neuman, M G, Kaganovsky, E, Kfir, B, Tur-Kaspa, RKlein, T. Circulating soluble cytochrome c in liver disease as a marker of apoptosis[J]. J Intern Med,2003,254(2):168-175
[175]黄伶.血清细胞色素c测定对危重病患者预警作用的临床研究[D].济南：山东大学,2006：1-35.
[176]Barczyk, K, Kreuter, M, Pryjma, J, Booy, E P, Maddika, S, Ghavami, S, Berdel, W E, Roth, JLos, M. Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy[J]. Int J Cancer,2005,116(2):167-173
[177]Marie-Jose'Mhawej, Cecile Brunet-Franc-Ois, Raphaelfonteneau, Damienernst, Virginieferre, Guy-Bartstan, Francois RaffiH.Moog, C. Apoptosis characterizes immunological failure of HFV infected patients[J]. Control Engineering Practice,2009,17:798-804
[178]English, R V, Johnson, C M, Gebhard, D HTompkins, M B. In vivo lymphocyte tropism of feline immunodeficiency virus[J]. J Virol,1993,67(9):5175-5186
[179]Schat, K A. Chicken anemia virus[J]. Curr Top Microbiol Immunol,2009,331:151-183
[180]Li, X M, Qian, P, Shi, D S, Jin, M L, Lan, S YChen, H C. [Induction or inhibition of apoptosis by pseudorabies virus ea strain in suckling piglets][J]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai),2003,35(4):325-330
[181]Mandrioli, L, Sarli, G, Panarese, S, Baldoni, SMarcato, P S. Apoptosis and proliferative activity in lymph node reaction in postweaning multisystemic wasting syndrome (PMWS)[J]. Vet Immunol Immunopathol,2004,97(1-2):25-37
[182]李超,伏圣博,刘华玲,马欣荣.细胞凋亡研究进展[J].世界科技研究与发展,2007,29(3)：45-53
[183]周建华,丛国正,高闪电,常惠芸.细胞凋亡的研究进展[J].生物技术通讯,2008,19(2)：274-276
[184]Gupta, S. Molecular steps of death receptor and mitochondrial pathways of apoptosis [J]. Life Sci, 2001,69(25-26):2957-2964
[185]Gloire, G, Charlier, EPiette, J. Regulation of CD95/APO-1/Fas-induced apoptosis by protein phosphatases[J]. Biochem Pharmacol,2008,76(11):1451-1458
[186]Brenner, D, Krammer, P HArnold, R. Concepts of activated T cell death[J]. Crit Rev Oncol Hematol,2008,66(1):52-64
[187]史毓杰,江振友,孙晗笑.HIV诱导T细胞凋亡机制研究进展[J].中国皮肤性病学杂志,2005,19(3)：179-182
[188]Desagher, SMartinou, J C. Mitochondria as the central control point of apoptosis [J]. Trends Cell Biol,2000,10(9):369-377
[189]Livak, K JSchmittgen, T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods,2001,25(4):402-408
[190]李燕华,李瑶宣,李吕力,王铁建.脑缺血大鼠水通道蛋白29mRNA表达与钙离子浓度的改变及其关系[J].临床神经病学杂志,2008,21(2)：129-132
[191]Kirkin, V, Joos, SZornig, M. The role of Bcl-2 family members in tumorigenesis[J]. Biochim Biophys Acta,2004,1644(2-3):229-249
[192]Vogel, M W. Cell death, Bcl-2, Bax, and the cerebellum[J]. Cerebellum,2002,1(4):277-287
[193]Mcconkey, D JOrrenius, S. Signal transduction pathways in apoptosis[J]. Stem Cells,1996, 14(6):619-631
[194]Scaffidi, C, Fulda, S, Srinivasan, A, Friesen, C, Li, F, Tomaselli, K J, Debatin, K M, Krammer, P HPeter, M E. Two CD95 (APO-1/Fas) signaling pathways [J]. EMBO J,1998,17(6):1675-1687
[195]Fischer, B, Coelho, D, Dufour, P, Bergerat, J P, Denis, J M, Gueulette, JBischoff, P. Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53-dependent apoptosis[J]. Biochem Biophys Res Commun,2003,306(2):516-522
[196]Lee, W Y, Lim, D S, Ko, S H, Park, Y J, Ryu, K S, Ahn, M Y, Kim, Y R, Lee, D WCho, C W. Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells[J]. J Photochem Photobiol B,2004,75(3):119-126
[197]Zhang, H, Zhao, D, Wang, ZZheng, D. Diazoxide preconditioning alleviates caspase-dependent and caspase-independent apoptosis induced by anoxia-reoxygenation of PC12 cells[J]. J Biochem, 2010,
[198]Bao, QShi, Y. Apoptosome:a platform for the activation of initiator caspases[J]. Cell Death Differ,2007,14(1):56-65
[199]Hocsak, E, Racz, B, Szabo, A, Pozsgai, E, Szigeti, A, Szigeti, E, Gallyas, F, Jr., Sumegi, B, Javor, SBellyei, S. TIP47 confers resistance to taxol-induced cell death by preventing the nuclear translocation of AIF and Endonuclease G[J]. Eur J Cell Biol,2010,89(11):853-861
[200]王瑞娟,彭瑞云,高亚兵,徐新萍,常公民,马俊杰,李杨,王水明AIF、Bax和Bcl-2在中子及γ射线照射致肠道损伤中的表达[J].解放军医学杂志,2009,34(11)：1356-1359
[201]于翠娟,孟艳玲,王成济,杨安钢.凋亡诱导因子是线粒体内介导核凋亡的最主要蛋白质之[J].生物化学与生物物理进展,2002,29(2)：177-179
[202]Norberg, E, Orrenius, SZhivotovsky, B. Mitochondrial regulation of cell death:processing of apoptosis-inducing factor (AIF)[J]. Biochem Biophys Res Commun,396(1):95-100
[203]Green, D RReed, J C. Mitochondria and apoptosis[J]. Science,1998,281(5381):1309-1312
[204]Asher, E, Payne, C MBernstein, C. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy. II. Induction of non-classic apoptosis ("para-apoptosis") by tritiated thymidine[J]. Leuk Lymphoma,1995,19(1-2): 107-119
[205]French, L E, Hahne, M, Viard, I, Radlgruber, G, Zanone, R, Becker, K, Muller, CTschopp, J. Fas and Fas ligand in embryos and adult mice:ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover[J]. J Cell Biol,1996, 133(2):335-343
[206]Sproll, K C, Ballo, H, Hoffmann, T K, Scheckenbach, K, Koldovsky, U, Balz, V, Hafner, D, Ramp, UBier, H. Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human squamous cell carcinomas of the head and neck (SCCHN)?[J]. Oral Oncol,2009,45(1):69-84
[207]曾文军,王柳均,樊翌明,吴志华.二期梅毒患者外周血淋巴细胞凋亡及其Fas、FasL表达的研究[J].医学理论与实践,2008,21(6)：646-648
[208]Shrestha, BDiamond, M S. Fas ligand interactions contribute to CD8+T-cell-mediated control of West Nile virus infection in the central nervous system[J]. J Virol,2007,81(21):11749-11757
[209]Benhamla, T, Tirouche, Y D, Abaoub-Germain, ATheodore, F. [The onset of psychiatric disorders and Wilson's disease][J]. Encephale,2007,33(6):924-932
[210]李琪佳,王峰,付文娟,孙瑞军,白俊清,王志强.骨肉瘤组织FLIP和FADD及Caspase-8蛋白表达与细胞凋亡相关性的研究[J].中国肿瘤防治杂志,2009,16(22)：1797-1800
[211]Wong, B, Arron, JChoi, Y. T cell receptor signals enhance susceptibility to Fas-mediated apoptosis[J]. J Exp Med,1997,186(11):1939-1944
[212]Mizutani, Y, Yoshida, O, Ukimura, O, Kawauchi, A, Bonavida, BMiki, T. Prognostic significance of a combination of soluble Fas and soluble Fas ligand in the serum of patients with Ta bladder cancer[J]. Cancer Biother Radiopharm,2002,17(5):563-567
[213]关秀茹,刘晓民,高光强,崔丽娟,杜柏岩,辛晓敏.Fas系统介导的细胞凋亡与自身免疫性甲状腺疾病关系的研究[J].中华微生物学和免疫学杂志,2001,21(1)：74
[214]Blanco-Colio, L M, Martin-Ventura, J L, Tunon, J, Garcia-Camarero, T, Berrazueta, J REgido, J. Soluble Fas ligand plasma levels are associated with forearm reactive hyperemia in subjects with coronary artery disease:a novel biomarker of endothelial function?[J]. Atherosclerosis,2008, 201(2):407-412
[215]Dowd, D R, Ryerse, J S, Macdonald, P N, Miesfeld, R LKamradt, M C. Crosstalk during Ca2+-, cAMP-, and glucocorticoid-induced gene expression in lymphocytes [J]. Mol Cell Endocrinol,1997, 128(1-2):29-37
[216]Saitoh, M, Nagai, K, Yaguchi, T, Fujikawa, Y, Ikejiri, K, Yamamoto, S, Nakagawa, K, Yamamura, TNishizaki, T. Arachidonic acid peroxides induce apoptotic Neuro-2A cell death in association with intracellular Ca(2+) rise and mitochondrial damage independently of caspase-3 activation[J]. Brain Res,2003,991(1-2):187-194
[217]邓守恒,孙各琴,陈崇宏Ca2+、 cAMP、cGMP在硒化壳聚糖诱导的NB4细胞凋亡中的作用[J].陕西医学杂志,2007,36(4)：415-417
[218]Mcconkey, D JOrrenius, S. The role of calcium in the regulation of apoptosis[J]. Biochem Biophys Res Commun,1997,239(2):357-366
[219]Gordienko, D V, Harhun, M I, Kustov, M V, Pucovsky, VBolton, T B. Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+release induced by voltage-gated Ca2+entry[J]. Cell Calcium,2008,43(2): 122-141
[220]方以群,刘景昌,李斌,周时粉,张洪柱.高压氧对沙鼠脑缺血海马神经细胞Ca2+-ATP酶活力的影响[J].中华航海医学与高气压医学杂志,2006,13(3)：156-158
[221]王岚,吕家高,张存泰,程冕,刘念,阮燕菲,王琳.钙调蛋白激酶Ⅱ信号转导途径在血管紧张素Ⅱ致心肌肥大反应中的调控作用[J].华中科技大学学报(医学版),2009,38(1)：27-30
[222]张吉仲.藏药帕如热对实验动物脏腑cAMP、cGMP含量影响的实验研究[J].江西中医学院学报,2008,20(6)：56-57
[223]刘英学,赵长新,徐浩彦.精神分裂症患者血血浆和淋巴细胞中cAMP、cGMP水平[J].职业与健康,2006,26(12)：905-906
[224]叶华,郑学宝.半枝莲多糖对小鼠脾淋巴细胞cAMP含量的影响[J].广东医学院学报,2009,27(2)：124-125
[225]Su, Y, Huang, X, Raskovalova, T, Zacharia, L, Lokshin, A, Jackson, EGorelik, E. Cooperation of adenosine and prostaglandin E2 (PGE2) in amplification of cAMP-PKA signaling and immunosuppression[J]. Cancer Immunol Immunother,2008,57(11):1611-1623
[226]王丽蒋,宗勇,林映才,马现永,蒋守群.环腺苷酸(cAMP)及其抗病生物学作用[J].饲料工业,2009,30(7)：7-9
[227]Thomson, B J. Viruses and apoptosis[J]. Int J Exp Pathol,2001,82(2):65-76
[228]于学武.病毒感染诱导细胞凋亡分子机制的研究进展[J].现代畜牧兽医,2010,10(6)：79-82
[229]彭开松,佘锐萍.动物病毒与宿主细胞的细胞凋亡[J].中国兽医杂志,2004,40(11)：40-44
[230]Li, T, Qiu, Z, Zhang, L, Han, Y, He, W, Liu, Z, Ma, X, Fan, H, Lu, W, Xie, J, Wang, H, Deng, GWang, A. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome[J]. J Infect Dis,2004,189(4):648-651
[231]Zhou, Y HChen, Z. Is the immune system impaired in patients with severe acute respiratory syndrome?[J]. Clin Infect Dis,2004,38(6):921-922; author reply 922
[232]张庆玲,丁彦青,贺莉,王蔚,张进华,王慧君,蔡俊杰,耿舰,陆药丹,罗元龙SARS病变组织细胞凋亡检测及其意义[J].第一军医大学学报,2003,23(8)：770-773
[233]Jacotot, E, Krust, B, Callebaut, C, Laurent-Crawford, a G, Blanco, JHovanessian, a G. HIV-1 envelope glycoproteins-mediated apoptosis is regulated by CD4 dependent and independent mechanisms [J]. Apoptosis,1997,2(1):47-60
[234]陈耿,赵焱,包银莉,孟玲玲,田忠园,李桂平,华利忠,张书霞.PCV2对体外培养仔猪脾细胞分泌细胞因子的动态影响[J].兽医科技,2009,41(9)：58-60
[235]Reichmann, E. The biological role of the Fas/FasL system during tumor formation and progression[J]. Semin Cancer Biol,2002,12(4):309-315
[236]卢晓晔,钟雪云Caspases与细胞凋亡(综述)[J].暨南大学学报(医学版),2000,21(6)：121-124
[237]Shi, Y. Mechanisms of caspase activation and inhibition during apoptosis[J]. Mol Cell,2002, 9(3):459-470
[238]高旭辉.淋巴细胞钙通道及细胞内钙离子的研究进展[J].医学综述,2004,10(11)：641-643
[239]胡庭俊,梁纪兰,程富胜,陈吉祥张爱文.黄芪多糖对鸡脾脏淋巴细胞内游离钙离子浓度的影响[J].中兽医医药杂志,2001,(5)：4-6
[240]武建胜,董炳凤,廖圣宝.滋阴潜阳方对高血压大鼠淋巴细胞内PKA蛋白表达和cAMP水平的影响[J].安徽中医学院学报,2008,27(1)：46-48
[241]O'connell, P J, Wang, X, Leon-Ponte, M, Griffiths, C, Pingle, S CAhern, G P. A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells[J]. Blood,2006,107(3):1010-1017
[242]Roman, Y, Alfonso, A, Vieytes, M R, Ofuji, K, Satake, M, Yasumoto, TBotana, L M. Effects of Azaspiracids 2 and 3 on intracellular cAMP, [Ca2+], and pH[J]. Chem Res Toxicol,2004,17(10): 1338-1349
[243]Lipskaia, LLompre, a M. Alteration in temporal kinetics of Ca2+signaling and control of growth and proliferation[J]. Biol Cell,2004,96(1):55-68
[244]Gong, S L, Dong, L H, Liu, G W, Gong, P S, Lu, W T, Zhao, H G, Jia, X JZhao, Y. Effects of corticosterone, cAMP, cGMP, Ca2+, and protein kinase C on apoptosis of mouse thymocytes induced by X-ray irradiation[J]. Biomed Environ Sci,2008,21(2):167-172
[245]张秀娟,穆冲,岳金凤,季宇彬.从Ca2+通路研究紫草多糖促进小鼠淋巴细胞增殖的机制[J].中国现代药物应用,2007,1(24)：24-25
[246]郭国庆,沈伟哉.细胞凋亡调控的分子机制(综述)[J].暨南大学学报(医学版),2001,22(2)：20-23
[247]唐海林.钙离子信号与细胞凋亡关系的研究进展[J].南华大学学报医学版,2006,34(5)：663-666
[248]Jayaraman, T, Ondriasova, E, Ondrias, K, Harnick, D JMarks, a R. The inositol 1,4,5-trisphosphate receptor is essential for T-cell receptor signaling[J]. Proc Natl Acad Sci USA, 1995,92(13):6007-6011
[249]Xie, C Y, Yang, W, Li, M, Ying, J, Tao, S J, Li, K, Dong, J HWang, X S. Cell apoptosis induced by delta-elemene in colorectal adenocarcinoma cells via a mitochondrial-mediated pathway[J]. Yakugaku Zasshi,2009,129(11):1403-1413
[250]Elrod, J W, Wong, R, Mishra, S, Vagnozzi, R J, Sakthievel, B, Goonasekera, S A, Karch, J, Gabel, S, Farber, J, Force, T, Brown, J H, Murphy, EMolkentin, J D. Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice[J]. J Clin Invest,2010,120(10):3680-3687
[251]Oh, S H, Lee, B HLim, S C. Cadmium induces apoptotic cell death in WI 38 cells via caspase-dependent Bid cleavage and calpain-mediated mitochondrial Bax cleavage by Bcl-2-independent pathway[J]. Biochem Pharmacol,2004,68(9):1845-1855
[252]王虎.Ca2+与内质网途径的细胞凋亡[J].国际病理科学与临床杂志,2006,26(4)：283-290
[253]Rizzuto, R, Pinton, P, Ferrari, D, Chami, M, Szabadkai, G, Magalhaes, P J, Di Virgilio, FPozzan, T. Calcium and apoptosis:facts and hypotheses[J]. Oncogene,2003,22(53):8619-8627
[254]Csordas, G, Renken, C, Varnai, P, Walter, L, Weaver, D, Buttle, K F, Balla, T, Mannella, C AHajnoczky, G. Structural and functional features and significance of the physical linkage between ER and mitochondria[J]. J Cell Biol,2006,174(7):915-921
[255]Sedlak, T WSnyder, S H. Messenger molecules and cell death:therapeutic implications [J]. JAMA,2006,295(1):81-89
[256]薛全福,王振纲.钙离子和细胞凋亡及药物调控[J].中国全科医学,2009,12(6B)：1126-1128
[257]Braun, a PSchulman, H. The multifunctional calcium/calmodulin-dependent protein kinase: from form to function[J]. Annu Rev Physiol,1995,57:417-445
[258]Yadav, M, Roach, S KSchorey, J S. Increased mitogen-activated protein kinase activity and TNF-alpha production associated with Mycobacterium smegmatis-but not Mycobacterium avium-infected macrophages requires prolonged stimulation of the calmodulin/calmodulin kinase and cyclic AMP/protein kinase A pathways[J]. J Immunol,2004,172(9):5588-5597
[259]于芳,张安民,李渊,胡淑萍.持续游泳训练对大鼠杏仁核cAMP浓度的影响[J].山西农业大学学报(自然科学版),2010,30(2)：105-107
[260]司维柯,李鹏,姚婕.苦参碱对HepG2细胞代谢水平和基因水平的影响[J].第三军医大学学报,2002,24(11)：1346-1349
[261]赵富清,张翠岚,彭兆云,谢宁,桂质丹,邓小琳.五参素对小鼠脾淋巴细胞内cAMP和cGMP含量的影响及细胞毒性作用[J].南京军医学院学报,2003,25(1)：4-6
[262]王丽,蒋宗勇,林映才,马现永,蒋守群.环腺苷酸(cAMP)及其抗病生物学作用[J].饲料工业,2009,30(7)：7-9
[263]Ma, W, Qi, Z, Smigel, A, Walker, R K, Verma, RBerkowitz, G A. Ca2+, cAMP, and transduction of non-self perception during plant immune responses[J]. Proc Natl Acad Sci USA,2009,106(49): 20995-21000
[264]蒋林,冯元璋,王琴,周兴挺,杨得坡.芦荟乙酰化甘露聚糖对肉仔鸡cAMP/cGMP与免疫功能的影响[J].中国畜牧杂志,2005,41(12)：7-11
[265]顾洛,陈晓红cAMP在急性胃粘膜损害中的作用的研究[J].中国应用生理学杂志,1994,10(1)：85-88
[266]唐胜球,董小英,邹晓庭.环腺苷酸的研究及其在动物营养中的应用[J].中国畜牧杂志,2006,42(5)：53-56