绿原酸抗乳腺炎作用及机制研究
摘要
大肠杆菌等革兰氏阴性菌是乳腺炎常见的致病菌。这些革兰氏阴性菌中，能够使宿主机体组织器官受到损伤的主要致病因子是脂多糖（LPS）。LPS是革兰氏阴性菌细胞壁的特殊成分，其能够激活TLR4（Toll-like receptor4）信号转导通路，进而使宿主机体产生炎性反应，过氧化物酶增殖物激活受体（PPAR-γ）在这个过程中能够起到重要的调控作用。本课题以我国中草药中存在的天然成分绿原酸为研究对象，首先在小鼠乳腺炎模型上证实其对炎症的抑制效果，其次分别对绿原酸在小鼠乳腺上皮细胞和奶牛乳腺上皮细胞上抗炎机制进行研究，最后对其作用靶标进行初步确认，从而为兽医临床实践中抗炎治疗提供新思路，为相应抗炎药物的研发提供初步的实验数据和理论基础。
首先，通过LPS诱发小鼠来建立乳腺炎损伤模型。我们选取18只Balb/C小鼠，雌雄比例2:1，混养后自由交配受孕，雌鼠在泌乳5～7天后，将其随机分为2组，LPS刺激组和空白对照组，6只/组。LPS刺激组雌鼠在其第四对乳头处分别灌注LPS50μL（0.2mg/mL），在灌注24h后将其脱颈处死；空白对照组的雌鼠不进行任何处理。通过肉眼观察LPS刺激组雌鼠的乳腺组织的病理学变化；对获得的雌鼠乳腺组织分别制作组织病理学切片和MPO的免疫组织化学切片，观察乳腺的病理组织学变化和MPO在组织中的分布及活性；通过ELISA方法检测乳腺组织中TNF-α因子的表达水平。实验结果表明，与空白对照组相比，肉眼观察到LPS刺激组雌鼠的乳腺组织出现明显的发红、肿胀、充血等病理学变化；组织病理学光学显微镜观察到乳腺的腺泡壁明显增厚、水肿，腺泡腔存在大量的嗜中性粒细胞；乳腺中MPO的分布与活性明显增加；乳腺中TNF-α因子的表达水平显著增多。以上获得的数据与典型乳腺炎的指标完全一致，说明本实验成功建立了LPS诱发的小鼠乳腺炎损伤模型。
其次，利用所建立的LPS诱发小鼠乳腺炎损伤的模型，研究绿原酸对乳腺炎的保护效果及其作用机理。我们将获得的乳腺炎损伤模型雌鼠随机分为6组，12只/组，分别为LPS刺激组，LPS+绿原酸低、中、高（12.5、25、50mg/kg体重），LPS+DEX组（5.0mg/kg体重，阳性对照）和空白对照组。在LPS灌注前1h和灌注后12h分别通过腹腔注射绿原酸和DEX。观察乳腺组织的病理学变化和MPO的分布与活性；ELISA方法检测乳腺组织中TNF-α、IL-1β和IL-6等细胞因子的表达水平；Western blot方法检测绿原酸对TLR4和NF-κB信号通路的影响。实验结果显示，与LPS刺激组相比，绿原酸能够显著降低LPS诱发的小鼠乳腺组织的炎性损伤；减少MPO在乳腺组织中的分布，且MPO的活性也显著降低；TNF-α、IL-1β和IL-6细胞因子的蛋白表达水平也显著降低；TLR4和NF-κB信号通路的激活也受到绿原酸的抑制。以上实验结果证明绿原酸通过对TLR4和NF-κB信号通路的激活的抑制作用，实现对LPS诱发的小鼠乳腺炎损伤的保护作用。
再次，我们为进一步验证绿原酸对乳腺炎损伤的保护效果，对小鼠乳腺上皮细胞进行了分离培养，研究绿原酸对其保护作用及其作用机理。利用MTT方法检测绿原酸对小鼠乳腺上皮细胞的毒性作用；ELISA方法检测绿原酸对小鼠乳腺上皮细胞中TNF-α和IL-6细胞因子表达水平的影响。Western blot方法检测绿原酸对小鼠乳腺上皮细胞中NF-κB信号通路的影响。实验结果表明，绿原酸在12.5、25、50μg/mL的浓度下不会对小鼠乳腺上皮细胞产生毒性作用；绿原酸预处理细胞后能够明显降低TNF-α和IL-6蛋白表达水平；Western blot证实绿原酸是通过抑制小鼠乳腺上皮细胞中NF-κB信号通路的激活而发挥其抗炎作用的。
然后，我们又成功分离培养了奶牛乳腺上皮细胞，进一步研究绿原酸对乳腺炎本源动物细胞的保护作用及其作用机理。利用MTT方法检测绿原酸对奶牛乳腺上皮细胞的毒性作用； qRT-PCR方法检测绿原酸对奶牛乳腺上皮细胞中TNF-α、IL-1β和IL-6细胞因子表达水平的影响；Western blot方法检测绿原酸对奶牛乳腺上皮细胞中TLR4信号通路的影响。实验结果表明，绿原酸在12.5、25、50μg/mL的浓度下不会对奶牛乳腺上皮细胞产生毒性作用；绿原酸预处理细胞后能够明显降低TNF-α，IL-1β和IL-6蛋白表达水平；Western blot证实绿原酸是通过抑制小鼠乳腺上皮细胞中TLR4信号通路的激活而发挥其抗炎作用的。
最后，我们对绿原酸的抗炎作用靶点进行了初步确定。通过PPAR-γ配体结合实验和Western blot方法检测绿原酸对PPAR-γ的结合和激活作用情况。选用PPAR-γ特异性拮抗剂GW9662来阻断PPAR-γ激活作用，再检测绿原酸对LPS诱发的TLR4表达的影响。实验结果显示，绿原酸能够与PPAR-γ结合并激活，同时发现绿原酸对LPS诱发的TLR4表达的影响也能够被PPAR-γ特异性拮抗剂GW9662所阻断，表明绿原酸通过结合并激活PPAR-γ而发挥抗炎作用。因此，通过实验我们初步确定PPAR-γ可能是绿原酸在体内的抗炎作用靶点。
本实验对绿原酸的抗炎作用机理和作用靶标进行了初步探索性研究，发现绿原酸能够结合并激活PPAR-γ，从而使TLR4下调表达并对下游的NF-κB信号通路的激活起到抑制作用，最终使乳腺中TNF-α、IL-1β和IL-6等炎性因子的基因和蛋白表达水平均下降。以上实验结果提示，绿原酸在奶牛乳腺炎的治疗中可能具有潜在的应用前景。
Gram-negative bacteria such as E.coli is the major pathogenic bacteria thatcauses bovine mastitis. LPS, the main component of the outer membranes ofGram-negative bacteria, plays a key role in producing an inflammatory response. LPScould activate TLR4signaling pathway and induce inflammatory response. Studiesshowed that PPAR-γ played an important role in inflammatory response. In this study,we first confirmed the anti-inflammatory effects of chlorogenic acid in LPS-inducedmastitis in mice. Secondly, we investigated the anti-inflammatory mechanism ofchlorogenic acid on LPS-stimulated bovine and mouse mammary epithelial cells. Inthe last, the molecular targets of the anti-inflammatory actions of chlorogenic acidwere identified. All the results will provide the reference and experimental basis forprevention and treatment of bovine mastitis by anti-inflammatory medicine inveterinary clinical practice.
Firstly, the mouse mastitis model induced by LPS was established. The lactatingBalb/C mice of5-7d were random divided into two groups: control group and LPSgroup. The fourth pair mammary glands of the mice were infusion with LPS(0.2mg/ml,50μL) through the mammary duct.24h after LPS induction, the mice werekilled. The pathological and histopathological changes of mammary gland wereobserved. Meanwhile, the activity of MPO and the level of TNF-α was detected. Theresults showed that the mammary gland showed redness, swelling, and congestion inLPS group. Meanwhile, the mammary histological examination also indicated thatmammary tissues infused with LPS showed thickening and edema of the alveoluswalls and inflammatory cells infiltration. In addition, the level of TNF-α wassignificantly increased in LPS group. These results demonstrated that the mousemastitis model induced by LPS was successfully established.
Secondly, the mouse model of mastitis was induced by injection of LPS throughthe duct of mammary gland. Chlorogenic acid was administered intraperitoneally withthe dose of12.5,25,50mg/kg respectively1h before and12h after induction of LPS. In this study, the effect of chlorogenic acid on LPS-induced mice mastitis wasassessed through histopathological examination, myeloperoxidase (MPO) activityanalysis, ELISA assay, and western blot analysis. The results showed that chlorogenicacid significantly attenuated the activity of MPO and reduced TNF-α, IL-1β, and IL-6production compared with LPS group. Besides, western blot analysis showed thatchlorogenic acid could inhibit the expression of TLR4and the phosphorylation ofNF-κB and IκB induced by LPS. These results suggested that anti-inflammatoryeffects of chlorogenic acid against LPS-induced mastitis may be due to its ability toinhibit TLR4-mediated NF-κB signaling pathway. Therefore, chlorogenic acid may bea potent therapeutic reagent for the prevention of mastitis.
Thirdly, to further detect the protective effect of chlorogenic acid on mastitis, themouse mammary epithelial cells were used. The cells were stimulated with LPS in thepresence or absence of chlorogenic acid. The expression of pro-inflammartorycytokines TNF-α, IL-6and IL-1β were determined by ELISA. NF-κB and IκBα weredetermined by Western blotting. The results showed that chlorogenic aciddose-dependently inhibited the expression of TNF-α, IL-6and IL-1β inLPS-stimulated mouse mammary epithelial cells. Western blot analysis showed thatchlorogenic acid suppressed LPS-induced NF-κB activation, IκBa degradation.
We also detected the protective effect of chlorogenic acid on LPS-stimulatedbovine mammary epithelial cells. The cells were stimulated with LPS in the presenceor absence of chlorogenic acid. The expression of pro-inflammartory cytokines TNF-α,IL-6and IL-1β were determined by qRT-PCR. TLR4, NF-κB and IκBα weredetermined by Western blotting. The results showed that chlorogenic aciddose-dependently inhibited the expression of TNF-α, IL-6and IL-1β inLPS-stimulated bovine mammary epithelial cells. Western blot analysis showed thatchlorogenic acid suppressed LPS-induced TLR4signaling pathway.
In the last, molecular targets of chlorogenic acid was identified. The bindingaffinity and activating of PPAR-γ were detected by PPAR-γ ligand binding assays andWestern blotting. Meanwhile, to detect whether the effects of chlorogenic acid onTLR4expression is dependent on PPAR-γ activation, GW9662, the specific PPAR-γantagonist was used. Then the cells were stimulated by LPS and TLR4expression was detected. The results showed that chlorogenic acid could bind and activate PPAR-γ.Furthermore, the inhibition effects of TLR4by chlorogenic acid can be reversed byGW9662, a specific antagonist for PPAR-γ. These results suggest that PPAR-γ may bethe anti-inflammatory targets of chlorogenic acid.
In conclusion, these results suggest that chlorogenic acid activates PPAR-γ,thereby attenuating TLR4expression and TLR4mediated NF-κB activation and therelease of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. These findings suggestthat chlorogenic acid may be a therapeutic agent against inflammatory diseases. Allthe results revealed that emodin may be used as a potential candidate in treatment ofmastitis.
首先，通过LPS诱发小鼠来建立乳腺炎损伤模型。我们选取18只Balb/C小鼠，雌雄比例2:1，混养后自由交配受孕，雌鼠在泌乳5～7天后，将其随机分为2组，LPS刺激组和空白对照组，6只/组。LPS刺激组雌鼠在其第四对乳头处分别灌注LPS50μL（0.2mg/mL），在灌注24h后将其脱颈处死；空白对照组的雌鼠不进行任何处理。通过肉眼观察LPS刺激组雌鼠的乳腺组织的病理学变化；对获得的雌鼠乳腺组织分别制作组织病理学切片和MPO的免疫组织化学切片，观察乳腺的病理组织学变化和MPO在组织中的分布及活性；通过ELISA方法检测乳腺组织中TNF-α因子的表达水平。实验结果表明，与空白对照组相比，肉眼观察到LPS刺激组雌鼠的乳腺组织出现明显的发红、肿胀、充血等病理学变化；组织病理学光学显微镜观察到乳腺的腺泡壁明显增厚、水肿，腺泡腔存在大量的嗜中性粒细胞；乳腺中MPO的分布与活性明显增加；乳腺中TNF-α因子的表达水平显著增多。以上获得的数据与典型乳腺炎的指标完全一致，说明本实验成功建立了LPS诱发的小鼠乳腺炎损伤模型。
其次，利用所建立的LPS诱发小鼠乳腺炎损伤的模型，研究绿原酸对乳腺炎的保护效果及其作用机理。我们将获得的乳腺炎损伤模型雌鼠随机分为6组，12只/组，分别为LPS刺激组，LPS+绿原酸低、中、高（12.5、25、50mg/kg体重），LPS+DEX组（5.0mg/kg体重，阳性对照）和空白对照组。在LPS灌注前1h和灌注后12h分别通过腹腔注射绿原酸和DEX。观察乳腺组织的病理学变化和MPO的分布与活性；ELISA方法检测乳腺组织中TNF-α、IL-1β和IL-6等细胞因子的表达水平；Western blot方法检测绿原酸对TLR4和NF-κB信号通路的影响。实验结果显示，与LPS刺激组相比，绿原酸能够显著降低LPS诱发的小鼠乳腺组织的炎性损伤；减少MPO在乳腺组织中的分布，且MPO的活性也显著降低；TNF-α、IL-1β和IL-6细胞因子的蛋白表达水平也显著降低；TLR4和NF-κB信号通路的激活也受到绿原酸的抑制。以上实验结果证明绿原酸通过对TLR4和NF-κB信号通路的激活的抑制作用，实现对LPS诱发的小鼠乳腺炎损伤的保护作用。
再次，我们为进一步验证绿原酸对乳腺炎损伤的保护效果，对小鼠乳腺上皮细胞进行了分离培养，研究绿原酸对其保护作用及其作用机理。利用MTT方法检测绿原酸对小鼠乳腺上皮细胞的毒性作用；ELISA方法检测绿原酸对小鼠乳腺上皮细胞中TNF-α和IL-6细胞因子表达水平的影响。Western blot方法检测绿原酸对小鼠乳腺上皮细胞中NF-κB信号通路的影响。实验结果表明，绿原酸在12.5、25、50μg/mL的浓度下不会对小鼠乳腺上皮细胞产生毒性作用；绿原酸预处理细胞后能够明显降低TNF-α和IL-6蛋白表达水平；Western blot证实绿原酸是通过抑制小鼠乳腺上皮细胞中NF-κB信号通路的激活而发挥其抗炎作用的。
然后，我们又成功分离培养了奶牛乳腺上皮细胞，进一步研究绿原酸对乳腺炎本源动物细胞的保护作用及其作用机理。利用MTT方法检测绿原酸对奶牛乳腺上皮细胞的毒性作用； qRT-PCR方法检测绿原酸对奶牛乳腺上皮细胞中TNF-α、IL-1β和IL-6细胞因子表达水平的影响；Western blot方法检测绿原酸对奶牛乳腺上皮细胞中TLR4信号通路的影响。实验结果表明，绿原酸在12.5、25、50μg/mL的浓度下不会对奶牛乳腺上皮细胞产生毒性作用；绿原酸预处理细胞后能够明显降低TNF-α，IL-1β和IL-6蛋白表达水平；Western blot证实绿原酸是通过抑制小鼠乳腺上皮细胞中TLR4信号通路的激活而发挥其抗炎作用的。
最后，我们对绿原酸的抗炎作用靶点进行了初步确定。通过PPAR-γ配体结合实验和Western blot方法检测绿原酸对PPAR-γ的结合和激活作用情况。选用PPAR-γ特异性拮抗剂GW9662来阻断PPAR-γ激活作用，再检测绿原酸对LPS诱发的TLR4表达的影响。实验结果显示，绿原酸能够与PPAR-γ结合并激活，同时发现绿原酸对LPS诱发的TLR4表达的影响也能够被PPAR-γ特异性拮抗剂GW9662所阻断，表明绿原酸通过结合并激活PPAR-γ而发挥抗炎作用。因此，通过实验我们初步确定PPAR-γ可能是绿原酸在体内的抗炎作用靶点。
本实验对绿原酸的抗炎作用机理和作用靶标进行了初步探索性研究，发现绿原酸能够结合并激活PPAR-γ，从而使TLR4下调表达并对下游的NF-κB信号通路的激活起到抑制作用，最终使乳腺中TNF-α、IL-1β和IL-6等炎性因子的基因和蛋白表达水平均下降。以上实验结果提示，绿原酸在奶牛乳腺炎的治疗中可能具有潜在的应用前景。
Gram-negative bacteria such as E.coli is the major pathogenic bacteria thatcauses bovine mastitis. LPS, the main component of the outer membranes ofGram-negative bacteria, plays a key role in producing an inflammatory response. LPScould activate TLR4signaling pathway and induce inflammatory response. Studiesshowed that PPAR-γ played an important role in inflammatory response. In this study,we first confirmed the anti-inflammatory effects of chlorogenic acid in LPS-inducedmastitis in mice. Secondly, we investigated the anti-inflammatory mechanism ofchlorogenic acid on LPS-stimulated bovine and mouse mammary epithelial cells. Inthe last, the molecular targets of the anti-inflammatory actions of chlorogenic acidwere identified. All the results will provide the reference and experimental basis forprevention and treatment of bovine mastitis by anti-inflammatory medicine inveterinary clinical practice.
Firstly, the mouse mastitis model induced by LPS was established. The lactatingBalb/C mice of5-7d were random divided into two groups: control group and LPSgroup. The fourth pair mammary glands of the mice were infusion with LPS(0.2mg/ml,50μL) through the mammary duct.24h after LPS induction, the mice werekilled. The pathological and histopathological changes of mammary gland wereobserved. Meanwhile, the activity of MPO and the level of TNF-α was detected. Theresults showed that the mammary gland showed redness, swelling, and congestion inLPS group. Meanwhile, the mammary histological examination also indicated thatmammary tissues infused with LPS showed thickening and edema of the alveoluswalls and inflammatory cells infiltration. In addition, the level of TNF-α wassignificantly increased in LPS group. These results demonstrated that the mousemastitis model induced by LPS was successfully established.
Secondly, the mouse model of mastitis was induced by injection of LPS throughthe duct of mammary gland. Chlorogenic acid was administered intraperitoneally withthe dose of12.5,25,50mg/kg respectively1h before and12h after induction of LPS. In this study, the effect of chlorogenic acid on LPS-induced mice mastitis wasassessed through histopathological examination, myeloperoxidase (MPO) activityanalysis, ELISA assay, and western blot analysis. The results showed that chlorogenicacid significantly attenuated the activity of MPO and reduced TNF-α, IL-1β, and IL-6production compared with LPS group. Besides, western blot analysis showed thatchlorogenic acid could inhibit the expression of TLR4and the phosphorylation ofNF-κB and IκB induced by LPS. These results suggested that anti-inflammatoryeffects of chlorogenic acid against LPS-induced mastitis may be due to its ability toinhibit TLR4-mediated NF-κB signaling pathway. Therefore, chlorogenic acid may bea potent therapeutic reagent for the prevention of mastitis.
Thirdly, to further detect the protective effect of chlorogenic acid on mastitis, themouse mammary epithelial cells were used. The cells were stimulated with LPS in thepresence or absence of chlorogenic acid. The expression of pro-inflammartorycytokines TNF-α, IL-6and IL-1β were determined by ELISA. NF-κB and IκBα weredetermined by Western blotting. The results showed that chlorogenic aciddose-dependently inhibited the expression of TNF-α, IL-6and IL-1β inLPS-stimulated mouse mammary epithelial cells. Western blot analysis showed thatchlorogenic acid suppressed LPS-induced NF-κB activation, IκBa degradation.
We also detected the protective effect of chlorogenic acid on LPS-stimulatedbovine mammary epithelial cells. The cells were stimulated with LPS in the presenceor absence of chlorogenic acid. The expression of pro-inflammartory cytokines TNF-α,IL-6and IL-1β were determined by qRT-PCR. TLR4, NF-κB and IκBα weredetermined by Western blotting. The results showed that chlorogenic aciddose-dependently inhibited the expression of TNF-α, IL-6and IL-1β inLPS-stimulated bovine mammary epithelial cells. Western blot analysis showed thatchlorogenic acid suppressed LPS-induced TLR4signaling pathway.
In the last, molecular targets of chlorogenic acid was identified. The bindingaffinity and activating of PPAR-γ were detected by PPAR-γ ligand binding assays andWestern blotting. Meanwhile, to detect whether the effects of chlorogenic acid onTLR4expression is dependent on PPAR-γ activation, GW9662, the specific PPAR-γantagonist was used. Then the cells were stimulated by LPS and TLR4expression was detected. The results showed that chlorogenic acid could bind and activate PPAR-γ.Furthermore, the inhibition effects of TLR4by chlorogenic acid can be reversed byGW9662, a specific antagonist for PPAR-γ. These results suggest that PPAR-γ may bethe anti-inflammatory targets of chlorogenic acid.
In conclusion, these results suggest that chlorogenic acid activates PPAR-γ,thereby attenuating TLR4expression and TLR4mediated NF-κB activation and therelease of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. These findings suggestthat chlorogenic acid may be a therapeutic agent against inflammatory diseases. Allthe results revealed that emodin may be used as a potential candidate in treatment ofmastitis.
引文
[1] Murphy, S. C., Cranker, K., Senyk, G. F., Barbano, D. M., Saeman, A. I. Galton,D. M. et al. Influence of bovine mastitis on lipolysis and proteolysis in milk [J].J. Dairy Sci.1998,71:65-69.
[2] Treece, J. M., Morse, G. E., Levy, C. et al. Lipid analysis of bovine teat canalkeratin [J]. J. Dairy Sci.1966,49:1240.
[3] Capuco, A. V., S. A. Bright, J. W. Pankey, D. L. Wood, R. H. Miller, J. Bitman.etal. Increased susceptibility to intramammary infection following removal of teatcanal keratin[J]. J. Dairy Sci.1992,75:2126.
[4] Jones, G. M.. Understanding the basics of mastitis. Virginia CooperativeExtension. Publication No.404-233. Virginia State University, USA.2006pp:1-7.
[5] Zhao X, Lacasse P. et al Mammary tissue damage during bovine mastitis: causesand control[J]. Journal of animal science,2008,86:57-65.
[6] Kapur, M. P., Anshusharma, Bahardwal, R. M. et al. Bacteriology of clinicalmastitis in Buffaloes [J]. Buffalo Bull.1992,11:32-35.
[7] Ahmed, M. N. Studies on strain of Staph. Aureus isolated from cases of mastitisin buffalo. MSc Thesis, Univ. Agri., Faisalabad, Pakistan.1966.
[8] Philpot, W. N., Nickerson, S. C.. Mastitis: Counter Attack. Westfalia Surge LLC:Illinois, USA.1999.
[9] Oliveira, S. S., Po′voa, D. C., Nascimento, J. S., Pereira, M. S. V., Siqueira, J. P.,Bastos, M. C. F., et al. Antimicrobial substances produced by Staphylococcusaureus strains isolated from cattle in Brazil[J]. Letters in Applied Microbiology.1998.27:229–234.
[10] Quinn, P. J., Carter, M. E., Markey, B., Carter, G. R.et al. Clinical VeterinaryMicrobiology [M]. Harcourt Publishers Ltd.: London.1999.
[11] Schroeder, J. W. Mastitis Control Programs: Bovine Mastitis and MilkingManagement Fargo: North Dakota State University Agriculture and UniversityExtension. Available from: http://www.ag.ndsu.edu/pubs/ansci/dairy/as1129w.htm.[Accessed25May2009].
[12] Schukken, Y. H., Tikofsky, L. Zadoks, R. N. Environmental control for mastitisprevention, milk quality and food safety. In: Hogeveen, H.(ed.), Mastitis indairy production Current knowledge and future solutions, WageningenAcademic Publishers, The Netherlands,2005, pp.109-114.
[13] Nascimento, J. D. S., Fagundes, P. C., Brito, M. A. V. D. P., Netto dos Santos, K.R., Bastos, M. D. et al. Production of bacteriocins by coagulase-negativestaphylococci involved in bovine mastitis [J]. vet. Microbiol.2005,106:61-71.
[14] Owens, W. N., Ray, C. H., Watts, J. L., Tancey, R J. et al.. Comparison ofsuccess of antibiotic therapy during lactation and result of antimicrobialsusceptibility test for bovine mastitis [J]. J.Dairy.Sci.1997,80:313-317.
[15] Kaliwal, B.B, M. M. Kurjogi. Prevalence and antimicrobial susceptibility ofbacteria isolated from bovine mastitis [J]. Advances in applied science research.2011,2(6):229-235.
[16] Moon, J.S., Lee, A. R., Kang, H. M., Lee, E. S., Joo, Y. S., Park, Y. H., Kim, M.N. Koo, H. C. Antibiogram and coagulase diversity in staphylococcalenterotoxin producing Staphylococcus aureus from bovine mastitis [J].J.Dairy.Sci.2006,90:1716-1724.
[17] Anakalo, S. A., G. Gathoni Tura, M. Mileah. Prevalence of bovine mastitisamongst small holder dairy herds in keya [J]. Isreal.J.Vet.Med.2004,80:307-312.
[18] Barefoot, S. F, G. A. Grinstead. Bacteriocins from dairy Propionibacteria andinducible bacteriocins of lactic acid bacteria, in: Bacteriocins of lactic acidbacteria (eds. D. G. Hoover, and l. R. Steenson), academic press, new york.2004,219–231.
[19] Jack, R. W., J. R. Tagg, B. Ray. Bacteriocins of gram-positive bacteria [J].Microbiol. Rev.1995,59:171-200.
[20] Cotter, P. D., C. Hill, R. P. Ross. Bacterial lantibiotics: strategies to improvetherapeutic potential, current protein and peptide science.2005,6:61-75.
[21] Cotter, P. D., C. Hill, R. P. Ross. Bacteriocins: Developing innate immunity forfood [J].Nature Rev. Microbiol.2005,3:777-788.
[22] Franz, C. M. A. P., M. J. Van Belkum, R. W. Worobo, J. C. Vederas, M. E. Stiles.Characterization of the genetic locus responsible for production and immunityof carnobacteriocin a: the immunity gene confers crossprotection to enterocinb [J]. Microbiol.2000,146:621–631.
[23] Franz, C. M. A. P., R. W. Worobo, E. N. Quadri, U. Schillinger, W. H. Holzapfel,J. C.Vederas, M. E. Stiles.. Atypical genetic locus associated with constitutiveproduction of enterocin b by Enterococcus faecium bfe900. Appl [J]. Environ.Microbiol.1999,65:2170–2178.
[24] Muriana, P.M. Luchansky, J.B. Biochemical methods for purification ofbacteriocins. In Bacteriocins of Lactic Acid Bacteria ed. Hoover, D.G. andSteenson, L.R.1993, pp.41–61. San Diego: Academic Press, Inc.
[25] Jones, G. M.. Understanding the basics of mastitis. Virginia CooperativeExtension. Publication No.404-233. Virginia State University, USA.2006, pp:1-7.
[26] Khan, M. Z. Khan A. Z.. Basic facts of mastitis in dairy animals: A review [J].Review article Pakistan Vet. J.2006,26(4):204-208.
[27] Kaliwal, B.B, M. M. Kurjogi. Prevalence and antimicrobial susceptibility ofbacteria isolated from bovine mastitis [J]. Advances in applied science research.2011,2(6):229-235.
[28] Rupp, R., Boichard, D. Genetics of resistance to mastitis in dairy cattle [J]. VetRes.2003,34(5):671-688.
[29]张振国.中药乳头灌注剂治疗临床型奶牛乳腺炎的研究[J];东北农业大学,2009.
[30]耿梅英,薛爱红,贾亚池.常用中药防治奶牛乳房炎病原菌效果研究[J].今日畜牧兽医,2006,(04):3-4.
[31] Amritha.G. Kulkarni, B. B. Kaliwal. BOVINE MASTITIS: A REVIEW [J].International Journal of Recent Scientific Research.2013,4(5):542-548.
[32] Janeway CA Jr, Medzhitov R. Innate immune recognition [J]. Annu RevImmunol2002,20:197–216.
[33] Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms andpathways [J]. Immunol Rev2000,173:89–97.
[34] Raetz CR, Whitfield C. Lipopolysaccharide endotoxins [J]. Annu Rev Biochem2002,71:635–700.
[35] Pugin J, Schurer-Maly CC, Leturcq D, Moriarty A, Ulevitch RJ, Tobias PS.Lipopolysaccharide activation of human endothelial and epithelial cells ismediated by lipopolysaccharide-binding protein and soluble CD14[J]. Proc NatlAcad Sci USA1993,90:2744–2748.
[36] Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F. Toll-likereceptor-4mediates lipopolysaccharide-induced signal transduction [J]. J biolChem.1999,274:10689–10692.
[37] Akira S, Takeda K. Toll-like receptor signalling [J]. Nat Rev Immunol.2004,4:499–511.
[38] Maeshima N, Fernandez RC. Recognition of lipid A variants by the TLR4-MD-2receptor complex [J]. Front Cell Infect Microbiol.2013,3:3.
[39] Trent MS, Stead CM, Tran AX, Hankins JV. Diversity of endotoxin and itsimpact on pathogenesis [J]. J Endotoxin Res.2006,12:205–223.
[40] TAKEDA K, AKIRA S. Regulation of innate immune responses by Toll-likereceptors [J]. Jpn J Infect Dis,2001,54(6):209-19.
[41] HSU L C, PARK J M, ZHANG K Z, et al. The protein kinase PKR is requiredfor macrophage apoptosis after activation of Toll-like receptor4[J]. Nature,2004,428(6980):341-5.
[42] Ulevitch RJ, Tobias PS. Receptor-dependent mechanisms of cell stimulation bybacterial endotoxin.Annu Rev Immunol1995;13:437–457.
[43] Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J. etal.Resistance to endotoxin shock and reduced dissemination of gramnegativebacteria in CD14-deficient mice [J]. Immunity.1996,4:407–414.
[44] ADEREM A, ULEVITCH R J. Toll-like receptors in the induction of the innateimmune response [J]. Nature,2000,406(6797):782-7.
[45] NAGAI Y, AKASHI S, NAGAFUKU M, et al. Essential role of MD-2in LPSresponsiveness and TLR4distribution [J]. Nat Immunol,2002,3(7):667-72.
[46] JANEWAY C A, JR., MEDZHITOV R. Innate immune recognition [J]. AnnuRev Immunol,2002,20(197-216.
[47] LU Y C, YEH W C, OHASHI P S. LPS/TLR4signal transduction pathway [J].Cytokine,2008,42(2):145-51.
[48] MEDZHITOV R, PRESTON-HURLBURT P, JANEWAY C A, JR. A humanhomologue of the Drosophila Toll protein signals activation of adaptiveimmunity [J]. Nature,1997,388(6640):394-7.
[49] Janssens S, Beyaert R. A universal role for MyD88in TLR/IL-1R-mediatedsignaling [J]. Trends Biochem Sci.2002,7:474–482
[50] ADEREM A, ULEVITCH R J. Toll-like receptors in the induction of the innateimmune response [J]. Nature,2000,406(6797):782-7.
[51] FITZGERALD K A, ROWE D C, BARNES B J, et al. LPS-TLR4signaling toIRF-3/7and NF-kappaB involves the toll adapters TRAM and TRIF [J]. J ExpMed,2003,198(7):1043-55.
[52] YAMAMOTO M, SATO S, HEMMI H, et al. Role of adaptor TRIF in theMyD88-independent toll-like receptor signaling pathway [J]. Science,2003,301(5633):640-3.
[53] OGANESYAN G, SAHA S K, GUO B, et al. Critical role of TRAF3in theToll-like receptor-dependent and-independent antiviral response [J]. Nature,2006,439(7073):208-11.
[54] VALLABHAPURAPU S, KARIN M. Regulation and function of NF-kappaBtranscription factors in the immune system [J]. Annu Rev Immunol,2009,27(693-733.
[55] GHOSH G, WANG V Y, HUANG D B, et al. NF-kappaB regulation: lessonsfrom structures [J]. Immunol Rev,2012,246(1):36-58.
[56] HOFFMANN A, NATOLI G, GHOSH G. Transcriptional regulation via theNF-kappaB signaling module [J]. Oncogene,2006,25(51):6706-16.
[57] PEARSON G, ROBINSON F, BEERS GIBSON T, et al. Mitogen-activatedprotein (MAP) kinase pathways: regulation and physiological functions [J].Endocr Rev,2001,22(2):153-83.
[58] CHEN R H, SARNECKI C, BLENIS J. Nuclear localization and regulation oferk-and rsk-encoded protein kinases [J]. Mol Cell Biol,1992,12(3):915-27.
[59] MOON S K, CHA B Y, KIM C H. ERK1/2mediates TNF-alpha-induced matrixmetalloproteinase-9expression in human vascular smooth muscle cells via theregulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway[J]. J Cell Physiol,2004,198(3):417-27.
[60] CARTER A B, MONICK M M, HUNNINGHAKE G W. Both Erk and p38kinases are necessary for cytokine gene transcription [J]. Am J Respir Cell MolBiol,1999,20(4):751-8.
[61] KUAN C Y, YANG D D, ROY D R S, et al. The Jnk1and Jnk2protein kinasesare required for regional specific apoptosis during early brain development [J].Neuron,1999,22(4):667-76.
[62] KENNEDY N J, DAVIS R J. Role of JNK in tumor development [J]. Cell Cycle,2003,2(3):199-201.
[63] BENNETT B L, SATOH Y, LEWIS A J. JNK: a new therapeutic target fordiabetes [J]. Curr Opin Pharmacol,2003,3(4):420-5.
[64] Beom Seok Park. Jie-Oh Lee. Recognition of lipopolysaccharide pattern byTLR4complexes [J]. Experimental&Molecular Medicine.2013,45, e66.
[65] P. M lgaard, H. Ravn. Evolutionary aspects of caffeoyl ester distribution inDicotyledons [J]. Phytochemistry.1988,27(8):2411–2421.
[66] S.A.deMoura,G.Negri,A.Salatino. et al. Aqueousextract of brazilian greenpropolis: primary components, evaluation of inflammation and wound healingby using subcutaneous implanted sponges [J]. Evidence-Based Complementaryand Alternative Medicine.2011,(748283):1-8
[67] D.Tang, H. J. Li, J. Chen, C. W. Guo, P. Li. Rapidand simple method forscreening of natural antioxidants from Chinese herb Flos Lonicerae Japonicaeby DPPH-HPLC-DADTOF/MS [J]. Journal of Separation Science.2008,31(20):3519-3526.
[68] N.Nuengchamnong, K. Krittasilp, K. Ingkaninan. Rapid screening andidentification of antioxidants in aqueous extracts of Houttuynia cordata usingLC-ESI-MS coupled with DPPH assay [J]. Food Chemistry.2009,117(4):750-756.
[69] Z. Chen, J. Zhang, G. Chen. Simultaneous determination of flavones andphenolic acids in the leaves of Ricinus communis Linn. by capillaryelectrophoresis with amperometric detection [J]. Journal of Chromatography B:Analytical Technologies in the Biomedical and Life Sciences.2008,863(1):101-106.
[70] M.D.dosSantos, M. C. Almeida, N. P. Lopes, G. E. P.de Souza. Evaluation ofthe anti-inflammatory, analgesic and antipyretic activities of the naturalpolyphenol chlorogenic acid [J]. Biological and Pharmaceutical Bulletin.2006,29(11):2236-2240.
[71] R. Kaur, U. Sharma, B. Singh, S. Arora. Antimutagenic and antioxidantcharacteristics of Chukrasia tabularis a Juss extracts [J]. International Journal ofToxicology.2011,30(1):21-34.
[72] J. H. Lee, J. H. Park, Y. S. Kim, Y. Han. Chlorogenic acid, a polyphenoliccompound, treats mice with septic arthritis caused by Candida albicans [J].International Immunopharmacology.2008,8(12):1681–1685.
[73] U. H. Jin, J. Y. Lee, S. K. Kang et al. A phenolic compound,5-caffeoylquinicacid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9inhibitor: Isolation and identification from methanol extract of Euonymusalatus[J]. Life Sciences.2005,77(22):2760-2769.
[74] S. M. Huang, H. C. Chuang, C. H. Wu, G. C. Yen. Cytoprotective effects ofphenolic acids on methylglyoxal-induced apoptosis in Neuro-2A cells [J].Molecular Nutrition&Food Research.2008,52(8):940-949.
[75] Mingbao Lin, Wan Gong, Qian Chen, Lijuan Sun, Yingchao Wang, Xiaohui Fan.Evaluation of the Potential Sensitization of Chlorogenic Acid: A Meta-Analysis[J]. Evidence-Based Complementary and Alternative Medicine.2013,(208467):1-9.
[76] Pirjo Mattila，HeHstrom J. Phenolic acids in potatoes, vegetables, and some oftheir products [J]. Journal of Food Composition and Analysis.2006,19:205-211.
[77]郭巧生,房海灵,申海进.不同产地野菊花中绿原酸咖啡酸和蒙花苷含量[J].中国中药杂志.2010,35(9):1160-1163.
[78]冯彬彬,王小翠,张建海等.不同产地金银花与山银花中绿原酸含量的比较研究[J].安徽农业科学.2012,40(2):729-730.
[79]王亚琴.杜仲叶有效成分的地理学研究[J].广东药学院学报.2000,16(3):173-176.
[80]金则新,李钧敏,朱小燕.夏腊梅总黄酮总绿原酸含量及其环境因子相关性分析[J].浙江大学学报(理学版).2007,34(4):459-464.
[81]伍庆,王兴宁,夏品华等.土壤养分因子对杜仲有效成分含量影响研究[J].安徽农业科学.2008,36(25):11002-11004.
[82]樊艳平,姚延椿,赵全保.不同月份元宝枫叶内黄酮绿原酸含量的变化[J].中国农学通报.2006,22(7):157-159.
[83]孙淑芳,沈学根,张新凤等.采收期对杭白菊4个主栽品种功效成分的影响[J].中国中药杂志.2011,36(21):2945-2949.
[84]赵静,杨俊霞,焦永康等.不同基因型杜仲叶片中绿原酸含量的检测[J].安徽农业科学.2011,39(4):2103-2104.
[85]刘宝臣,李瑞国,侯文锐.忍冬不同器官中绿原酸的提取及含量测定[J].安徽农业科学.2011,39(32):19734-19735.
[86]青梅,王素巍,杨慧等.金银忍冬茎和果实中绿原酸的提取及含量测定[J].内蒙古农业大学学报(自然科学版).2011,32(1):281-284.
[87] StrackD, Gross W. Properties and Activity Changes of Chlorogenic Acid:Glucaric Acid Caffeoyl transferase From Tomato (Lycopersicon esculentum)[J].Plant Physiol.1990,92:41-47.
[88] Niggeweg R，Michael A. J.，Martin C. Engineering plantswith increased levelsof the antioxidant chlorogenic acid[J]. Nat Biotechnol.2004,22:746-754.
[89] Rhodes M J C，Wooltorton LS C. The enzymatic conversion of hydroxycinn-amic acid stop-coumaroyl quinic and chlorogenic acids in tomato[J].Phytochem.1976,15:947-951.
[90] Ulbrich B，Zenk M H. Partial purification and properties of hydroxycinnamoyl-CoA: quinate hydroxycinnamoyl transferase from higher plants[J]. Phytochem.1979,18:929-933.
[91] Xiaoxiao Peng, Weidong Li, Wenquan Wang, et al. Cloning and characterizationof a cDNA coding a hydroxycinnamoyl-CoA quinate hydroxycinnamoyltransferase involved in chlorogenic acid biosynthesis in Lonicerajaponica[J].PlantaMed.2010,76:1921.
[92]张丹,李章万,姜焱. HPLC测定金银花茵陈及其10种中成药中绿原酸的含量[J].药物分析杂志.1996,16(2):83.
[93] Dorrell D G. Chlorogenic acid content of meal from cultivatial sunflower[J].Cropscience.1976,16:422.
[94]林缎嫦,宋劲诗,吴应照.金银花中绿原酸的提取工艺探讨[J].中成药.1994,16(7):16-17
[95]赵昱,赵军,李湘萍等.咖啡酰奎尼酸类化合物研究进展[J].中国中药杂志.2006,32(11):869-874.
[96]张鞍灵,马琼,高锦明等.绿原酸及其类似物与生物活性[J].中草药.2001,32(2):173-176.
[97] Rodriguez de Sotillo D V，Hadley M. Chlorogenic acid modifies plasma andliver concentrations of: cholesterol，triacylglycerol，andmineralsin(fa/fa) Zuckerrats[J]. JNutr Biochem.2002,13:717-726.
[98] Chlopcikova S, Psotova J, Miketova P, et al. Chemoprotective effect of plantphenolics against anthracycline-induced toxicityon rat cardiomyocytes. Part I.Silymarinandits flavonolignans[J]. Phytother Res.2004,18:107-110.
[99]樊宏伟,肖大伟,余黎等.金银花及其有机酸类化合物的体外抗血小板聚集作用[J].中国医院药学杂志.2006,26(2):145-147.
[100]Kasai H, Fukada S, Yamaizumi Z, et al. Action of chlorogenic acid in vegetablesand fruits as an inhibitor of8-hydroxydeoxyguanosine formation in vitro and ina rat carcino genesis model[J]. Food ChemToxicol.2000,38:467-471.
[101]胡宗福,于文利,赵亚平.绿原酸清除活性氧和抗脂质过氧化的研[J].食品科学.2006,27(2):128-130.
[102]张俊敬,罗云峰,颜景奇等.咖啡和绿茶的抗氧化活性研究[J].生物物理学报.2008,24(6):435-444.
[103]童珊珊,余江南,徐希明等.薄层色谱-生物自显影技术测定绵茵陈提取液中绿原酸的含量并评价其抗氧化活性[J].中国药学杂志.2009,44(22):1738-1741.
[104]Iwai K, Kishimoto N, KakinoY, et al. In vitro antioxidative effects andtyrosinase inhibitory activities of seven hydroxycinnamoyl derivatives in greencoffee beans[J]. J Agric Food Chem.2004,52:4893-4898.
[105]SanRHC, Chan RIM. Inhibitory effect of phenolic compounds on a flatoxinB1metabolism and induced mutagenesis[J]. Mutation Res.1987,177:229-239.
[106]Wood A W, Hung M T, Chang H L, et al. Inhibition of the mutagenicity ofbay-regiondiol epoxides of polycyclicaromatic hydrocarbons by naturallyoccurring plant phenols; Exceptional activity of ellagic acid[J]. Proc Natl AcadSci USA.1982,79:5513-5517.
[107]Jiang Y, Kusama K, Sakata K, et al. Inhibitory effects of chlorogenic acid bycholrogenic acid in humanoral tumor cell lines[J]. Phytomedicine.2000,7:483-491.
[108]Pellati F, Benvenuti S, MagroL, et al. Analysis of phenolic compounds andradical scavenging activity of Echinaceaspp[J]. J Pharm Biomed Anal.2004,35:289-301.
[109]李丽静,王继彦,王岩等.返魂草提取物及其有效成分抗病毒作用的研究[J].中国中医基础医学杂志.2005,11(8):585-587.
[110]王林青,张红英,崔保安等.金银花山银花绿原酸类提取物体外抗NDV作用研究[J].中国农学通报.2011,27(19):277-282.
[111]Chiang L C, Chiang W, Chang M Y, et al. Antiviral activity of Plantago majorextracts and related compounds in vitro[J]. Antiviral Res.2002,55:53-62.
[112]屈景年,莫运春,刘梦琴等.金银花中绿原酸一步提取法及绿原酸抗菌活性[J].化学世界.2005,3:167-169.
[113]梅林.秀山金银花叶茎中绿原酸的检测及其抑菌作用研究[J].中国药业.2007,16(3):5-7.
[114]王海燕,张仕华,赵谋明等.烟草绿原酸分离纯化及其抑菌性研究[J].现代食品科技.2008,24(3):233-237.
[115]Frank J, Kamal-Eldin A, RazAan A, et al. The dietary hydroxycinnamate caffeicacid and its conjugate chlorogenic acid increase vitamin E and cholesterolconcentrations in SpragueDawley rats[J]. J Argric Food Chem.2003,51:2526-2531.
[116]Shimoda H, Seki E, Aitani M. Inhibitory effect of green coffee bean extract onfat accumulation and body weight gain in mice[J]. BMC Complement AlternMed.2006,17(6):9.
[117]王强,陈东辉,邓文龙.金银花提取物对血脂与血糖的影响[J].中药药理与临床.2007,23(3):40-42.
[118]Chiang L C, Chiang W, Chang M Y, et al. Antileukemic activity of selectednatural products inTaiwan[J]. Am J Chin Med.2003,31:37-46.
[119]Bandyopadhyay G, Biswas T, RoyKC, et al. Chlorogenic acid inhibits Bcr-Abltyrosinekinase and triggers p38mitogen-activated protein kinase-dependentapoptosis in chronic myelogenous leukemic cells[J]. Blood.2004,104:2514-2522
[120]毛水春,顾谦群,崔承彬等.中药大血藤中酚类化学成分及其抗肿瘤活性[J].中国药物化学杂志.2004,14(6):326-330.
[121]古莹.绿原酸对白血病细胞的抑制作用及其作用机制的研究[D].浙江大学硕士毕业论文.2007:3-6.
[122]马力,唐凤敏,曾天舒等.菊花多糖和绿原酸免疫调节作用的研究[J].医药导报.2008,27(10):1168-1170
[123]Wang J，Mazza G. Effects of anthocyanins and other phenolic compounds on theproduction of tumor necrosis factor alpha in LPS/IFN-gamma-activatedRAW2647macrophages[J]. J Agric Food Chem.2002,50(15):4183-4189.
[124]Jin X H, Ohgam I K, Shiratorik, et al. Effects of blue honeysuckle(LoniceraaeruleaL.) extract onlipopolysaccharide-induced inflammationin vitro and in vivo[J]. Exp Eye Res.2006,82(5):860-867.
[125]Gong J, Chen S S. Polyphenolic antioxidants inhibit peptide presentation byantigen-presenting cells[J]. Int Immunopharmacol.2003,3:1841-1852.
[126]Wu H Z, Luo J, Yin Y X, et al. Effects of chlorogenic acid, an active compoundactivating calcineurin, purified from Flos Lonicerae on macrophage[J]. ActaPharmacol Sin.2004,25:1685-1689.
[127]刘玉敏.向日葵叶中绿原酸的提取及降血糖药效学研究[D].延吉:延边大学硕士论文，2006:4-6.
[128]Andrade-Cetto A, Wiedenfeld H. Hypoglycemic effect of Cecropiaobtusifolia-onstreptozoto in diabetic rats[J]. J Ethnopharmacol.2001,78:145-149.
[129]Krakauer T. The polyphenol chlorogenic acid inhibits staphylococcal exotoxininduced inflammatory cytokines and chemokines[J]. ImmunopharmacolImmunotoxicol.2002,24:113-119.
[130]Ina H, Yamada K, MatsumotoK, et al. Effects of benzyl glucoside andchlorogenic acid from Prunus mumeonadrenocortico tropic hormone (ACTH)and catecholamine levels in plasma of experimental menopausal model rats[J].Biol PharmBull.2004,27:136-137.
[131]Mueller E, Sarraf P, Tontonoz P, Evans RM, Martin KJ, Zhang M. et al.Terminal differentiation of human breast cancer through PPAR gamma [J]. MolCell.1998,1:465–470.
[132]Escher P, Wahli W. Peroxisome proliferator-activated receptors: insight intomultiple cellular functions [J]. Mutat Res.2000,448:121–138.
[133]Lazennec G, Canaple L, Saugy D, Wahli W. Activation of peroxisomeproliferator-activated receptors (PPARs) by their ligands and protein kinase Aactivators [J]. Mol Endocrinol.2000,14:1962–1975.
[134]Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphanreceptors to drug discovery [J]. J Med Chem.2000,43:527–550.
[135]Diep QN, Schiffrin EL. Increased expression of peroxisomeproliferator-activated receptor-alpha and-gamma in blood vessels ofspontaneously hypertensive rats [J]. Hypertension.2001,38:249-254.
[136]Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L. et al. Expression andfunction of PPARgamma in rat and human vascular smooth muscle cells [J].Circulation.2000,101:1311-1318.
[137]Park KS, Ciaraldi TP, Abrams-Carter L, Mudaliar S, Nikoulina SE, Henry RR.PPAR-gamma gene expression is elevated in skeletal muscle of obese and type IIdiabetic subjects [J]. Diabetes.1997,46:1230-1234.
[138]Rangwala SM, Lazar MA. Peroxisome proliferator-activated receptor gamma indiabetes and metabolism [J]. Trends Pharmacol Sci.2004,25:331–336.
[139]Sharma AM, Staels B. Review: peroxisome proliferator-activated receptorgamma and adipose tissue-understanding obesity-related changes in regulationof lipid and glucose metabolism [J]. J Clin Endocrinol Metab.2007,92:386-395.
[140]Fergus P McCarthy, Aoife C Delany, Louise C Kenny, Sarah K Walsh.PPAR-gamma possible drug target for complicated pregnancies[J]. BritishJournal of Pharmacology.2013,168:1074-1085.
[141]Debril MB, Renaud JP, Fajas L, et al. The pleiotropic functions of peroxisomeproliferator-activated receptor gamma [J].J Mol Med.2001,79:30-47.
[142]Fajas L, Debril MB, Auwerx J. Peroxisome proliferator-activatedreceptorgamma: from adipogenesis to carcinogenesis.J Mol Endocrino l2001;27:1–9.
[143]Desreumaux P, Dubuquoy L, Nutten S, et al. Attenuation of colon inflammationthrough activators of the retinoid X receptor (RXR)/peroxisomeproliferator-activated receptor gamma (PPARgamma) heterodimer. A basis fornew therapeutic strategies [J]. J Exp Med.2001,193:827-38.
[144]Marx N, Mach F, Sauty A, et al. Peroxisome proliferator-activatedreceptorgamma activators inhibit IFN-gamma-induced expression of the Tcell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells[J]. J Immunol.2000,164:6503-8.
[145]Harris SG, Phipps RP. The nuclear receptor PPAR gamma is expressed by mouseT lymphocytes and PPAR gamma agonists induce apoptosis [J]. Eur J Immunol.2001,31:1098-105.
[146]Hontecillas R, Wannemeulher MJ, Zimmerman DR, et al. Nutritional regulationof porcine bacterial-induced colitis by conjugated linoleicacid [J]. J Nutr.2002,132:2019-2027.
[147]Bassaganya-Riera J, Reynolds K, Martino-Catt S, et al. Activation of PPARgamma and delta by conjugated linoleic acid mediates protection fromexperimental inflammatory bowel disease [J]. Gastroenterology.2004,127:777-791.
[148]Alonso L, Cuesta EP, Gilliland SE. Production of free conjugated linoleic acidby Lactobacillus acidophilus and Lactobacillus casei of human intestinal origin[J]. J Dairy Sci.2003,86:1941-6
[149]Cuzzocrea S, Pisano B, Dugo L, et al. Rosiglitazone and15-deoxydelta12,14-prostaglandin J2, ligands of the peroxisome proliferator-activatedreceptor-gamma (PPAR-gamma), reduce ischaemia/reperfusion injury of the gut[J]. Br J Pharmacol.2003,140:366-76.
[150]Fitzgerald GA, Loll P. COX in a crystal ball: current status and future promise ofprostaglandin research [J]. J Clin Invest.2001,107:1335-7.
[151]Schopfer FJ, Lin Y, Baker PR, et al. Nitrolinoleic acid: an endogenousperoxisome proliferator-activated receptor gamma ligand [J]. Proc Natl Acad SciUSA.2005,102:2340-2345.
[152]Lewis JD, Lichtenstein GR, Stein RB, et al. An open-label trial of thePPARgamma ligand rosiglitazone for active ulcerative colitis [J]. Am JGastroenterol.2001,96:3323-3328.
[153]L Dubuquoy, C Rousseaux, X Thuru, L Peyrin-Biroulet, O Romano, P Chavatte,M Chamaillard, P Desreumaux. PPARc AS A NEW THERAPEUTIC TARGETIN INFLAMMATORY BOWEL DISEASES [J]. Gut.2006,55:1341-1349.
[154]E. Mor′an-Salvador, M. L′opez-Parra, V. Garc′a-Alonso et al. Role for PPARγin obesity-induced hepatic steatosis as determined by hepatocyte-andmacrophage-specific conditional knockouts [J]. FASEB Journal.2011,25(8):2538-2550.
[155]V. Gazit, J. Huang, A. Weymann, and D. A. Rudnick. Analysis of the role ofhepatic PPARγ expression during mouse liver regeneration [J]. Hepatology.2012,56(4):1489-1498.
[156]Z. Chen, P. A. Vigueira, N. Qi. et al. Insulin resistance and metabolicderangements in obese mice are ameliorated by a novel peroxisomeproliferator-activated receptor γ-sparing thiazolidinedione [J]. Journal ofBiological Chemistry.2012,287(28):23537-23548.
[157]Z.Han,T.Zhu,X.Liu. et al.15-deoxy-Δ12,14-prostaglandin J2reducesrecruitment of bone marrow-derived monocyte/macrophages in chronic liverinjury in mice [J]. Hepatology.2012,56(1):350–360.
[158]P. Escher, O. Braissant, S. Basu-Modak, L. Michalik, W. Wahli, B. Desvergne.Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting andrefeeding [J]. Endocrinology.2001,142(10):4195-4202.
[159]W. Su, C. R. Bush, B. M. Necela. et al. Differential expression, distribution, andfunction of PPAR-γ in the proximal and distal colon [J]. PhysiologicalGenomics.2007,30(3):342-353.
[160]G. D. Girnun, W. M. Smith, S. Drori et al. APC-dependent suppression of coloncarcinogenesis by PPARγ [J]. Proceedings of the National Academy ofSciences of the United States of America.2002,99(21):13771-13776.
[161]N. P.Evans, S. A. Misyak, E. M. Schmelz, A. J. Guri, R. Hontecillas, J.Bassaganya-Riera. Conjugated linoleic acid ameliorates inflammation-inducedcolorectal cancer in mice through activation of PPARγ [J]. Journal of Nutrition.2010,140(3):515-521.
[162]M. Adachi, R. Kurotani, K. Morimura et al. Peroxisome proliferator activatedreceptorγ in colonic epithelial cells protects against experimental inflammatorybowel disease [J]. Gut.2006,55(8):1104-1113.
[163]D. Kelly, J. I. Campbell, T. P. King. et al. Commensalanaerobic gut bacteriaattenuate inflammation by regulating nuclearcytoplasmic shutting of PPAR-γand ReIA [J]. Nature Immunology.2004,5(1):104-112.
[164]A. J. Guri, S. K. Mohapatra, W. T. Horne, R. Hontecillas, J. Bassaganya-Riera.The Role of T cell PPAR γin mice with experimental inflammatory boweldisease [J]. BMC Gastroenterology.2010,10:60.
[165]R.Hontecillas, W. T. Horne, M. Climent. et al. Immunoregulatory mechanismsof macrophage PPAR-γ in mice with experimental inflammatory bowel disease[J]. Mucosal Immunology.2011,4(3):304-313.
[166]R. Hontecillas, J. Bassaganya-Riera. Peroxisome proliferator-activated receptorγ is required for regulatory CD4+T cell-mediated protection against colitis [J].Journal of Immunology.2007,178(5):2940–2949.
[167]T. Breidert, J. Callebert, M. T. Heneka, G. Landreth, J. M. Launay, E. C. Hirsch.Protective action of the peroxisome proliferator-activated receptor-γ agonistpioglitazone in a mouse model of Parkinson’s disease [J]. Journal ofNeurochemistry.2002,82(3):615-624.
[168]T. Dehmer, M. T. Heneka, M. Sastre, J. Dichgans, J. B. Schulz. Protection bypioglitazone in the MPTP model of Parkinson’s disease correlates with IκBαinduction and block of NF κ B and iNOS activation [J]. Journal ofNeurochemistry.2004,88(2):494-501.
[169]F. Penas, G. A. Mirkin, E. Hovsepian et al.,“PPARγ ligand treatment inhibitscardiac inflammatory mediators induced by infection with different lethalitystrains of Trypanosoma cruzi [J]. Biochimica et Biophysica Acta.2013,1832(1):239-248.
[170]E. Hovsepian, G. A. Mirkin, F. Penas, A. Manzano, R. Bartrons, N. B. Goren.Modulation of inflammatory response and parasitism by15-Deoxy-Δ12,14prostaglandin J2in Tr ypanosoma cruzi-infected cardiomyocytes[J].International Journal for Parasitology.2011,41(5):553-562.
[171]A. Qu, Y. M. Shah, S. K. Manna, F. J. Gonzalez. Disruption of endothelialperoxisome proliferator-activated receptor γ accelerates diet-inducedatherogenesis in LDL receptor-null mice [J]. Arteriosclerosis, Thrombosis, andVascular Biolog.2012,32(1):65-73.
[172]A. T. Reddy, S. P. Lakshmi, J. M. Kleinhenz, R. L. Sutliff, C. M. Hart, R. C.Reddy. Endothelial cell peroxisome proliferator-activated receptorγ reducesendotoxemic pulmonary inflammation and injury [J]. Journal of Immunology.2012,189(11):5411-5420.
[173]B. Buitenhuis, C. M. R ntved, S. M. Edwards, K. L. Ingvartsen, P. S rensen. Indepth analysis of genes and pathways of the mammary gland involved in thepathogenesis of bovine Escherichia coli-mastitis [J]. BMC Genomics.2011,12:130.
[174]D. Yang, H. Yang, W. Li. et al. Generation of PPARγmonoallelic knockout pigsvia zinc-finger nucleases and nucleartransfer cloning [J]. Cell Research.2011,21(6):979-982.
[175]Stéphane Mandard, David Patsouris. Nuclear Control of the InflammatoryResponse in Mammals by Peroxisome Proliferator-Activated Receptors [J].PPAR Research.2013,(613864):1-23.
[176]Wang LH, Yang XY, Zhang X, Huang J, Hou J, Li J, Xiong H, Mihalic K, Zhu H,Xiao W, Farrar WL. Transcriptional inactivation of STAT3by PPARgammasuppresses IL-6-responsive multiple myeloma cells [J]. Immunity.2004,20:205-218.
[177]Nadiminty N, Lou W, Lee SO, Lin X, Trump DL, Gao AC. Stat3activation ofNF-{kappa}B p100processing involves CBP/p300-mediated acetylation [J].Proc Natl Acad Sci USA.2006,103:7264-7269.
[178]Wang LH, Yang XY, Zhang X, Farrar WL. Inhibition of adhesive interactionbetween multiple myeloma and bone marrow stromal cells by PPARgammacross talk with NF-kappaB and C/EBP [J]. Blood.2007,110:4373-4384.
[179]Jung WK, Park IS, Park SJ, Yea SS, Choi YH, Oh S, Park SG, Choi IW. The15-deoxyDelta12,14-prostaglandin J2inhibits LPS-stimulated AKT andNF-kappaB activation and suppresses interleukin-6in osteoblast-like cellsMC3T3E-1[J]. Life Sci.2009,85:46-53.
[180]Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, WillsonTM, Rosenfeld MG, Glass CK. A SUMOylation-dependent pathway mediatestransrepression of inflammatory response genes by PPAR-gamma [J]. Nature.2005,437:759-763.
[181]Chearwae W, Bright JJ. PPARgamma agonists inhibit growth and expansion ofCD133+brain tumour stem cells [J]. Br J Cancer.2008,99:2044-2053.
[182]Ide H, Nakagawa T, Terado Y, Kamiyama Y, Muto S, Horie S. Tyk2expressionand its signaling enhances the invasiveness of prostate cancer cells [J]. BiochemBiophys Res Commun.2008,369:292-296.
[183]Schuster C, Muller M, Freissmuth M, Sexl V, Stoiber D. Commentary on H. Ideet al. Tyk2expression and its signaling enhances the invasiveness of prostatecancer cells [J]. Biochem Biophys Res Commun.2008,366:869-870.
[184]Sen B, Saigal B, Parikh N, Gallick G, Johnson FM. Sustained Src inhibitionresults in signal transducer and activator of transcription3(STAT3) activationand cancer cell survival via altered Janus-activated kinase-STAT3binding [J].Cancer Res.2009,69:1958-1965.
[185]Wang Z, Sun Y. Targeting p53for Novel Anticancer Therapy [J]. Transl Oncol.2010,3:1-12.
[186]Bai MH, Ma HB, Wang XJ, Liu XX, Xue XH, Xue FJ. Effects of activatedPPARgamma on the expression of PTEN gene in pancreatic cancer cells [J].2008,24:717-720.
[187]Dong YW, Wang XP, Wu K. Suppression of pancreatic carcinoma growth byactivating peroxisome proliferator-activated receptor gamma involvesangiogenesis inhibition [J]. World J Gastroenterol.2009,15:441-448.
[188]Gregory T. Robbinsand Daotai Nie. PPARgamma, Bioactive Lipids, and CancerProgression [J]. Front Biosci.2012,17:1816-1834.
[189]KOKAI-KUN J F, CHANTURIYA T, MOND J J. Lysostaphin as a treatment forsystemic Staphylococcus aureus infection in a mouse model [J]. J AntimicrobChemoth,2007,60(5):1051-9.
[190]ZHENG J M, WATSON A D, KERR D E. Genome-wide expression analysis oflipopolysaccharide-induced mastitis in a mouse model [J]. Infection andimmunity,2006,74(3):1907-15.
[191]CHANDLER R L. Experimental bacterial mastitis in the mouse [J]. Journal ofmedical microbiology,1970,3(2):273-82.
[192]BROUILLETTE E, MALOUIN F. The pathogenesis and control ofStaphylococcus aureus-induced mastitis: study models in the mouse [J].Microbes and Infection,2005,7(3):560-8.
[193]NOTEBAERT S, MEYER E. Mouse models to study the pathogenesis andcontrol of bovine mastitis. A review [J]. Vet Quart,2006,28(1):2-13.
[194]BANNERMAN D D, PAAPE M J, HARE W R, et al. Increased levels ofLPS-binding protein in bovine blood and milk following bacteriallipopolysaccharide challenge [J]. J Dairy Sci,2003,86(10):3128-37.
[195]OVIEDO-BOYSO J, VALDEZ-ALARCON J J, CAJERO-JUAREZ M, et al.Innate immune response of bovine mammary gland to pathogenic bacteriaresponsible for mastitis [J]. J Infection,2007,54(4):399-409.
[196]BANNERMAN D D, PAAPE M J, HARE W R, et al. Increased levels ofLPS-binding protein in bovine blood and milk following bacteriallipopolysaccharide challenge [J]. J Dairy Sci,2003,86(10):3128-37.
[197]LEE J W, PAAPE M J, ELSASSER T H, et al. Elevated milk soluble CD14inbovine mammary glands challenged with Escherichia coli lipopolysaccharide [J].J Dairy Sci,2003,86(7):2382-9.
[198]Alain, K., Karrow, N.A., Thibault, C., St-Pierre, J., Lessard, M., Bissonnette, N.,Osteopontin: an early innate immune marker ofEscherichia coli mastitis harborsgenetic polymorphisms with possible links with resistance to mastitis [J]. BMCGenomics.2009,10.
[199]Gonen, E., Vallon-Eberhard, A., Elazar, S., Harmelin, A., Brenner, O.,Rosenshine, I., Jung, S., Shpigel, N.Y. Toll-like receptor4is needed to restrictthe invasion of Escherichia coliP4into mammary gland epithelial cells in amurine model of acute mastitis [J]. Cell. Microbiol.2007,9:2826–2838.
[200]Gu, B.B., Miao, J.F., Zhu, Y.M., Deng, Y.E., Zou, S.X. Protective effect ofretinoid against endotoxin-induced mastitis in rats [J]. Inflamm. Res.2009,58:81-88.
[201]Zhu, W., Gu, B., Miao, J., Lu, J., Zou, S.,. Dectin1activation ofbeta-(1–3)/(1–6)-Dglucan produces an anti-mastitis effect in rats [J]. Inflamm.Res.2011,60:937-945.
[202]Bannerman, D.D. Pathogen-dependent induction of cytokines and other solubleinflammatory mediators during intramammary infection of dairy cows [J]. J.Anim. Sci.2009,87:10-25.
[203]Zheng, J., Watson, A.D., Kerr, D.E. Genome-wide expression analysis oflipopolysaccharide-induced mastitis in a mouse model. Infect. Immun [J].2006,74:1907-1915.
[204]Giebelen, I.A., van Westerloo, D.J., LaRosa, G.J., de Vos, A.F., van der Poll, T.Local stimulation of alpha7cholinergic receptors inhibits LPS-induced TNFalpha release in the mouse lung [J]. Shock.2007,28:700-703.
[205]Medzhitov, R., Kagan, J.C. Phosphoinositide-mediated adaptor recruitmentcontrols toll-like receptor signaling [J]. Cell.2006,125:943-955.
[206]GU B B, MIAO J F, FA Y M, et al. Retinoic acid attenuateslipopolysaccharide-induced inflammatory responses by suppressingTLR4/NF-kappa B expression in rat mammary tissue [J]. Internationalimmunopharmacology,2010,10(7):799-805.
[207]CHU X, SONG K, XU K, et al. Ceftiofur attenuates lipopolysaccharide-inducedacute lung injury [J]. International immunopharmacology,2010,10(5):600-604.
[208]XINMIN D, YUNYOU D, CHAOSHENG P, et al. Dexamethasone treatmentattenuates early seawater instillation-induced acute lung injury in rabbits [J].Pharmacological research: the official journal of the Italian PharmacologicalSociety,2006,53(4):372-379.
[209]Hichem Lahouassa, Etienne Moussay, Pascal Rainard, et al. Differentialcytokine and chemokine responses of bovinemammary epithelial cells toStaphylococcus aureus and Escherichia coli [J]. Cytokine.2007,38:12–21.
[210]Dilip Pate,l RauclA Almeida, John R Dunlap,et al. Oliver. Bovine lactoferrinserves as a molecular bridge for internalization of Streptococcus uberis intobovine mammary epithelial cells [J]. Veterinary Microbiology,2009,137:297-301.
[211]MUN L, JUN M S, KIM Y M, et al.7,8-didehydrocimigenol from Cimicifugaerhizoma inhibits TNF-alpha-induced VCAM-1but not ICAM-1expressionthrough upregulation of PPAR-gamma in human endothelial cells [J]. Food andChemical Toxicology,2011,49(1):166-72.
[212]SHENG X Y, ZHANG Y B, GONG Z W, et al. Improved Insulin Resistance andLipid Metabolism by Cinnamon Extract through Activation of PeroxisomeProliferator-Activated Receptors [J]. Ppar Research,2008.
[213]JI Y Y, LIU J T, WANG Z D, et al. PPAR gamma agonist, rosiglitazone,regulates angiotensin II-induced vascular inflammation through theTLR4-dependent signaling pathway [J]. Lab Invest,2009,89(8):887-902.
[2] Treece, J. M., Morse, G. E., Levy, C. et al. Lipid analysis of bovine teat canalkeratin [J]. J. Dairy Sci.1966,49:1240.
[3] Capuco, A. V., S. A. Bright, J. W. Pankey, D. L. Wood, R. H. Miller, J. Bitman.etal. Increased susceptibility to intramammary infection following removal of teatcanal keratin[J]. J. Dairy Sci.1992,75:2126.
[4] Jones, G. M.. Understanding the basics of mastitis. Virginia CooperativeExtension. Publication No.404-233. Virginia State University, USA.2006pp:1-7.
[5] Zhao X, Lacasse P. et al Mammary tissue damage during bovine mastitis: causesand control[J]. Journal of animal science,2008,86:57-65.
[6] Kapur, M. P., Anshusharma, Bahardwal, R. M. et al. Bacteriology of clinicalmastitis in Buffaloes [J]. Buffalo Bull.1992,11:32-35.
[7] Ahmed, M. N. Studies on strain of Staph. Aureus isolated from cases of mastitisin buffalo. MSc Thesis, Univ. Agri., Faisalabad, Pakistan.1966.
[8] Philpot, W. N., Nickerson, S. C.. Mastitis: Counter Attack. Westfalia Surge LLC:Illinois, USA.1999.
[9] Oliveira, S. S., Po′voa, D. C., Nascimento, J. S., Pereira, M. S. V., Siqueira, J. P.,Bastos, M. C. F., et al. Antimicrobial substances produced by Staphylococcusaureus strains isolated from cattle in Brazil[J]. Letters in Applied Microbiology.1998.27:229–234.
[10] Quinn, P. J., Carter, M. E., Markey, B., Carter, G. R.et al. Clinical VeterinaryMicrobiology [M]. Harcourt Publishers Ltd.: London.1999.
[11] Schroeder, J. W. Mastitis Control Programs: Bovine Mastitis and MilkingManagement Fargo: North Dakota State University Agriculture and UniversityExtension. Available from: http://www.ag.ndsu.edu/pubs/ansci/dairy/as1129w.htm.[Accessed25May2009].
[12] Schukken, Y. H., Tikofsky, L. Zadoks, R. N. Environmental control for mastitisprevention, milk quality and food safety. In: Hogeveen, H.(ed.), Mastitis indairy production Current knowledge and future solutions, WageningenAcademic Publishers, The Netherlands,2005, pp.109-114.
[13] Nascimento, J. D. S., Fagundes, P. C., Brito, M. A. V. D. P., Netto dos Santos, K.R., Bastos, M. D. et al. Production of bacteriocins by coagulase-negativestaphylococci involved in bovine mastitis [J]. vet. Microbiol.2005,106:61-71.
[14] Owens, W. N., Ray, C. H., Watts, J. L., Tancey, R J. et al.. Comparison ofsuccess of antibiotic therapy during lactation and result of antimicrobialsusceptibility test for bovine mastitis [J]. J.Dairy.Sci.1997,80:313-317.
[15] Kaliwal, B.B, M. M. Kurjogi. Prevalence and antimicrobial susceptibility ofbacteria isolated from bovine mastitis [J]. Advances in applied science research.2011,2(6):229-235.
[16] Moon, J.S., Lee, A. R., Kang, H. M., Lee, E. S., Joo, Y. S., Park, Y. H., Kim, M.N. Koo, H. C. Antibiogram and coagulase diversity in staphylococcalenterotoxin producing Staphylococcus aureus from bovine mastitis [J].J.Dairy.Sci.2006,90:1716-1724.
[17] Anakalo, S. A., G. Gathoni Tura, M. Mileah. Prevalence of bovine mastitisamongst small holder dairy herds in keya [J]. Isreal.J.Vet.Med.2004,80:307-312.
[18] Barefoot, S. F, G. A. Grinstead. Bacteriocins from dairy Propionibacteria andinducible bacteriocins of lactic acid bacteria, in: Bacteriocins of lactic acidbacteria (eds. D. G. Hoover, and l. R. Steenson), academic press, new york.2004,219–231.
[19] Jack, R. W., J. R. Tagg, B. Ray. Bacteriocins of gram-positive bacteria [J].Microbiol. Rev.1995,59:171-200.
[20] Cotter, P. D., C. Hill, R. P. Ross. Bacterial lantibiotics: strategies to improvetherapeutic potential, current protein and peptide science.2005,6:61-75.
[21] Cotter, P. D., C. Hill, R. P. Ross. Bacteriocins: Developing innate immunity forfood [J].Nature Rev. Microbiol.2005,3:777-788.
[22] Franz, C. M. A. P., M. J. Van Belkum, R. W. Worobo, J. C. Vederas, M. E. Stiles.Characterization of the genetic locus responsible for production and immunityof carnobacteriocin a: the immunity gene confers crossprotection to enterocinb [J]. Microbiol.2000,146:621–631.
[23] Franz, C. M. A. P., R. W. Worobo, E. N. Quadri, U. Schillinger, W. H. Holzapfel,J. C.Vederas, M. E. Stiles.. Atypical genetic locus associated with constitutiveproduction of enterocin b by Enterococcus faecium bfe900. Appl [J]. Environ.Microbiol.1999,65:2170–2178.
[24] Muriana, P.M. Luchansky, J.B. Biochemical methods for purification ofbacteriocins. In Bacteriocins of Lactic Acid Bacteria ed. Hoover, D.G. andSteenson, L.R.1993, pp.41–61. San Diego: Academic Press, Inc.
[25] Jones, G. M.. Understanding the basics of mastitis. Virginia CooperativeExtension. Publication No.404-233. Virginia State University, USA.2006, pp:1-7.
[26] Khan, M. Z. Khan A. Z.. Basic facts of mastitis in dairy animals: A review [J].Review article Pakistan Vet. J.2006,26(4):204-208.
[27] Kaliwal, B.B, M. M. Kurjogi. Prevalence and antimicrobial susceptibility ofbacteria isolated from bovine mastitis [J]. Advances in applied science research.2011,2(6):229-235.
[28] Rupp, R., Boichard, D. Genetics of resistance to mastitis in dairy cattle [J]. VetRes.2003,34(5):671-688.
[29]张振国.中药乳头灌注剂治疗临床型奶牛乳腺炎的研究[J];东北农业大学,2009.
[30]耿梅英,薛爱红,贾亚池.常用中药防治奶牛乳房炎病原菌效果研究[J].今日畜牧兽医,2006,(04):3-4.
[31] Amritha.G. Kulkarni, B. B. Kaliwal. BOVINE MASTITIS: A REVIEW [J].International Journal of Recent Scientific Research.2013,4(5):542-548.
[32] Janeway CA Jr, Medzhitov R. Innate immune recognition [J]. Annu RevImmunol2002,20:197–216.
[33] Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms andpathways [J]. Immunol Rev2000,173:89–97.
[34] Raetz CR, Whitfield C. Lipopolysaccharide endotoxins [J]. Annu Rev Biochem2002,71:635–700.
[35] Pugin J, Schurer-Maly CC, Leturcq D, Moriarty A, Ulevitch RJ, Tobias PS.Lipopolysaccharide activation of human endothelial and epithelial cells ismediated by lipopolysaccharide-binding protein and soluble CD14[J]. Proc NatlAcad Sci USA1993,90:2744–2748.
[36] Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F. Toll-likereceptor-4mediates lipopolysaccharide-induced signal transduction [J]. J biolChem.1999,274:10689–10692.
[37] Akira S, Takeda K. Toll-like receptor signalling [J]. Nat Rev Immunol.2004,4:499–511.
[38] Maeshima N, Fernandez RC. Recognition of lipid A variants by the TLR4-MD-2receptor complex [J]. Front Cell Infect Microbiol.2013,3:3.
[39] Trent MS, Stead CM, Tran AX, Hankins JV. Diversity of endotoxin and itsimpact on pathogenesis [J]. J Endotoxin Res.2006,12:205–223.
[40] TAKEDA K, AKIRA S. Regulation of innate immune responses by Toll-likereceptors [J]. Jpn J Infect Dis,2001,54(6):209-19.
[41] HSU L C, PARK J M, ZHANG K Z, et al. The protein kinase PKR is requiredfor macrophage apoptosis after activation of Toll-like receptor4[J]. Nature,2004,428(6980):341-5.
[42] Ulevitch RJ, Tobias PS. Receptor-dependent mechanisms of cell stimulation bybacterial endotoxin.Annu Rev Immunol1995;13:437–457.
[43] Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J. etal.Resistance to endotoxin shock and reduced dissemination of gramnegativebacteria in CD14-deficient mice [J]. Immunity.1996,4:407–414.
[44] ADEREM A, ULEVITCH R J. Toll-like receptors in the induction of the innateimmune response [J]. Nature,2000,406(6797):782-7.
[45] NAGAI Y, AKASHI S, NAGAFUKU M, et al. Essential role of MD-2in LPSresponsiveness and TLR4distribution [J]. Nat Immunol,2002,3(7):667-72.
[46] JANEWAY C A, JR., MEDZHITOV R. Innate immune recognition [J]. AnnuRev Immunol,2002,20(197-216.
[47] LU Y C, YEH W C, OHASHI P S. LPS/TLR4signal transduction pathway [J].Cytokine,2008,42(2):145-51.
[48] MEDZHITOV R, PRESTON-HURLBURT P, JANEWAY C A, JR. A humanhomologue of the Drosophila Toll protein signals activation of adaptiveimmunity [J]. Nature,1997,388(6640):394-7.
[49] Janssens S, Beyaert R. A universal role for MyD88in TLR/IL-1R-mediatedsignaling [J]. Trends Biochem Sci.2002,7:474–482
[50] ADEREM A, ULEVITCH R J. Toll-like receptors in the induction of the innateimmune response [J]. Nature,2000,406(6797):782-7.
[51] FITZGERALD K A, ROWE D C, BARNES B J, et al. LPS-TLR4signaling toIRF-3/7and NF-kappaB involves the toll adapters TRAM and TRIF [J]. J ExpMed,2003,198(7):1043-55.
[52] YAMAMOTO M, SATO S, HEMMI H, et al. Role of adaptor TRIF in theMyD88-independent toll-like receptor signaling pathway [J]. Science,2003,301(5633):640-3.
[53] OGANESYAN G, SAHA S K, GUO B, et al. Critical role of TRAF3in theToll-like receptor-dependent and-independent antiviral response [J]. Nature,2006,439(7073):208-11.
[54] VALLABHAPURAPU S, KARIN M. Regulation and function of NF-kappaBtranscription factors in the immune system [J]. Annu Rev Immunol,2009,27(693-733.
[55] GHOSH G, WANG V Y, HUANG D B, et al. NF-kappaB regulation: lessonsfrom structures [J]. Immunol Rev,2012,246(1):36-58.
[56] HOFFMANN A, NATOLI G, GHOSH G. Transcriptional regulation via theNF-kappaB signaling module [J]. Oncogene,2006,25(51):6706-16.
[57] PEARSON G, ROBINSON F, BEERS GIBSON T, et al. Mitogen-activatedprotein (MAP) kinase pathways: regulation and physiological functions [J].Endocr Rev,2001,22(2):153-83.
[58] CHEN R H, SARNECKI C, BLENIS J. Nuclear localization and regulation oferk-and rsk-encoded protein kinases [J]. Mol Cell Biol,1992,12(3):915-27.
[59] MOON S K, CHA B Y, KIM C H. ERK1/2mediates TNF-alpha-induced matrixmetalloproteinase-9expression in human vascular smooth muscle cells via theregulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway[J]. J Cell Physiol,2004,198(3):417-27.
[60] CARTER A B, MONICK M M, HUNNINGHAKE G W. Both Erk and p38kinases are necessary for cytokine gene transcription [J]. Am J Respir Cell MolBiol,1999,20(4):751-8.
[61] KUAN C Y, YANG D D, ROY D R S, et al. The Jnk1and Jnk2protein kinasesare required for regional specific apoptosis during early brain development [J].Neuron,1999,22(4):667-76.
[62] KENNEDY N J, DAVIS R J. Role of JNK in tumor development [J]. Cell Cycle,2003,2(3):199-201.
[63] BENNETT B L, SATOH Y, LEWIS A J. JNK: a new therapeutic target fordiabetes [J]. Curr Opin Pharmacol,2003,3(4):420-5.
[64] Beom Seok Park. Jie-Oh Lee. Recognition of lipopolysaccharide pattern byTLR4complexes [J]. Experimental&Molecular Medicine.2013,45, e66.
[65] P. M lgaard, H. Ravn. Evolutionary aspects of caffeoyl ester distribution inDicotyledons [J]. Phytochemistry.1988,27(8):2411–2421.
[66] S.A.deMoura,G.Negri,A.Salatino. et al. Aqueousextract of brazilian greenpropolis: primary components, evaluation of inflammation and wound healingby using subcutaneous implanted sponges [J]. Evidence-Based Complementaryand Alternative Medicine.2011,(748283):1-8
[67] D.Tang, H. J. Li, J. Chen, C. W. Guo, P. Li. Rapidand simple method forscreening of natural antioxidants from Chinese herb Flos Lonicerae Japonicaeby DPPH-HPLC-DADTOF/MS [J]. Journal of Separation Science.2008,31(20):3519-3526.
[68] N.Nuengchamnong, K. Krittasilp, K. Ingkaninan. Rapid screening andidentification of antioxidants in aqueous extracts of Houttuynia cordata usingLC-ESI-MS coupled with DPPH assay [J]. Food Chemistry.2009,117(4):750-756.
[69] Z. Chen, J. Zhang, G. Chen. Simultaneous determination of flavones andphenolic acids in the leaves of Ricinus communis Linn. by capillaryelectrophoresis with amperometric detection [J]. Journal of Chromatography B:Analytical Technologies in the Biomedical and Life Sciences.2008,863(1):101-106.
[70] M.D.dosSantos, M. C. Almeida, N. P. Lopes, G. E. P.de Souza. Evaluation ofthe anti-inflammatory, analgesic and antipyretic activities of the naturalpolyphenol chlorogenic acid [J]. Biological and Pharmaceutical Bulletin.2006,29(11):2236-2240.
[71] R. Kaur, U. Sharma, B. Singh, S. Arora. Antimutagenic and antioxidantcharacteristics of Chukrasia tabularis a Juss extracts [J]. International Journal ofToxicology.2011,30(1):21-34.
[72] J. H. Lee, J. H. Park, Y. S. Kim, Y. Han. Chlorogenic acid, a polyphenoliccompound, treats mice with septic arthritis caused by Candida albicans [J].International Immunopharmacology.2008,8(12):1681–1685.
[73] U. H. Jin, J. Y. Lee, S. K. Kang et al. A phenolic compound,5-caffeoylquinicacid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9inhibitor: Isolation and identification from methanol extract of Euonymusalatus[J]. Life Sciences.2005,77(22):2760-2769.
[74] S. M. Huang, H. C. Chuang, C. H. Wu, G. C. Yen. Cytoprotective effects ofphenolic acids on methylglyoxal-induced apoptosis in Neuro-2A cells [J].Molecular Nutrition&Food Research.2008,52(8):940-949.
[75] Mingbao Lin, Wan Gong, Qian Chen, Lijuan Sun, Yingchao Wang, Xiaohui Fan.Evaluation of the Potential Sensitization of Chlorogenic Acid: A Meta-Analysis[J]. Evidence-Based Complementary and Alternative Medicine.2013,(208467):1-9.
[76] Pirjo Mattila，HeHstrom J. Phenolic acids in potatoes, vegetables, and some oftheir products [J]. Journal of Food Composition and Analysis.2006,19:205-211.
[77]郭巧生,房海灵,申海进.不同产地野菊花中绿原酸咖啡酸和蒙花苷含量[J].中国中药杂志.2010,35(9):1160-1163.
[78]冯彬彬,王小翠,张建海等.不同产地金银花与山银花中绿原酸含量的比较研究[J].安徽农业科学.2012,40(2):729-730.
[79]王亚琴.杜仲叶有效成分的地理学研究[J].广东药学院学报.2000,16(3):173-176.
[80]金则新,李钧敏,朱小燕.夏腊梅总黄酮总绿原酸含量及其环境因子相关性分析[J].浙江大学学报(理学版).2007,34(4):459-464.
[81]伍庆,王兴宁,夏品华等.土壤养分因子对杜仲有效成分含量影响研究[J].安徽农业科学.2008,36(25):11002-11004.
[82]樊艳平,姚延椿,赵全保.不同月份元宝枫叶内黄酮绿原酸含量的变化[J].中国农学通报.2006,22(7):157-159.
[83]孙淑芳,沈学根,张新凤等.采收期对杭白菊4个主栽品种功效成分的影响[J].中国中药杂志.2011,36(21):2945-2949.
[84]赵静,杨俊霞,焦永康等.不同基因型杜仲叶片中绿原酸含量的检测[J].安徽农业科学.2011,39(4):2103-2104.
[85]刘宝臣,李瑞国,侯文锐.忍冬不同器官中绿原酸的提取及含量测定[J].安徽农业科学.2011,39(32):19734-19735.
[86]青梅,王素巍,杨慧等.金银忍冬茎和果实中绿原酸的提取及含量测定[J].内蒙古农业大学学报(自然科学版).2011,32(1):281-284.
[87] StrackD, Gross W. Properties and Activity Changes of Chlorogenic Acid:Glucaric Acid Caffeoyl transferase From Tomato (Lycopersicon esculentum)[J].Plant Physiol.1990,92:41-47.
[88] Niggeweg R，Michael A. J.，Martin C. Engineering plantswith increased levelsof the antioxidant chlorogenic acid[J]. Nat Biotechnol.2004,22:746-754.
[89] Rhodes M J C，Wooltorton LS C. The enzymatic conversion of hydroxycinn-amic acid stop-coumaroyl quinic and chlorogenic acids in tomato[J].Phytochem.1976,15:947-951.
[90] Ulbrich B，Zenk M H. Partial purification and properties of hydroxycinnamoyl-CoA: quinate hydroxycinnamoyl transferase from higher plants[J]. Phytochem.1979,18:929-933.
[91] Xiaoxiao Peng, Weidong Li, Wenquan Wang, et al. Cloning and characterizationof a cDNA coding a hydroxycinnamoyl-CoA quinate hydroxycinnamoyltransferase involved in chlorogenic acid biosynthesis in Lonicerajaponica[J].PlantaMed.2010,76:1921.
[92]张丹,李章万,姜焱. HPLC测定金银花茵陈及其10种中成药中绿原酸的含量[J].药物分析杂志.1996,16(2):83.
[93] Dorrell D G. Chlorogenic acid content of meal from cultivatial sunflower[J].Cropscience.1976,16:422.
[94]林缎嫦,宋劲诗,吴应照.金银花中绿原酸的提取工艺探讨[J].中成药.1994,16(7):16-17
[95]赵昱,赵军,李湘萍等.咖啡酰奎尼酸类化合物研究进展[J].中国中药杂志.2006,32(11):869-874.
[96]张鞍灵,马琼,高锦明等.绿原酸及其类似物与生物活性[J].中草药.2001,32(2):173-176.
[97] Rodriguez de Sotillo D V，Hadley M. Chlorogenic acid modifies plasma andliver concentrations of: cholesterol，triacylglycerol，andmineralsin(fa/fa) Zuckerrats[J]. JNutr Biochem.2002,13:717-726.
[98] Chlopcikova S, Psotova J, Miketova P, et al. Chemoprotective effect of plantphenolics against anthracycline-induced toxicityon rat cardiomyocytes. Part I.Silymarinandits flavonolignans[J]. Phytother Res.2004,18:107-110.
[99]樊宏伟,肖大伟,余黎等.金银花及其有机酸类化合物的体外抗血小板聚集作用[J].中国医院药学杂志.2006,26(2):145-147.
[100]Kasai H, Fukada S, Yamaizumi Z, et al. Action of chlorogenic acid in vegetablesand fruits as an inhibitor of8-hydroxydeoxyguanosine formation in vitro and ina rat carcino genesis model[J]. Food ChemToxicol.2000,38:467-471.
[101]胡宗福,于文利,赵亚平.绿原酸清除活性氧和抗脂质过氧化的研[J].食品科学.2006,27(2):128-130.
[102]张俊敬,罗云峰,颜景奇等.咖啡和绿茶的抗氧化活性研究[J].生物物理学报.2008,24(6):435-444.
[103]童珊珊,余江南,徐希明等.薄层色谱-生物自显影技术测定绵茵陈提取液中绿原酸的含量并评价其抗氧化活性[J].中国药学杂志.2009,44(22):1738-1741.
[104]Iwai K, Kishimoto N, KakinoY, et al. In vitro antioxidative effects andtyrosinase inhibitory activities of seven hydroxycinnamoyl derivatives in greencoffee beans[J]. J Agric Food Chem.2004,52:4893-4898.
[105]SanRHC, Chan RIM. Inhibitory effect of phenolic compounds on a flatoxinB1metabolism and induced mutagenesis[J]. Mutation Res.1987,177:229-239.
[106]Wood A W, Hung M T, Chang H L, et al. Inhibition of the mutagenicity ofbay-regiondiol epoxides of polycyclicaromatic hydrocarbons by naturallyoccurring plant phenols; Exceptional activity of ellagic acid[J]. Proc Natl AcadSci USA.1982,79:5513-5517.
[107]Jiang Y, Kusama K, Sakata K, et al. Inhibitory effects of chlorogenic acid bycholrogenic acid in humanoral tumor cell lines[J]. Phytomedicine.2000,7:483-491.
[108]Pellati F, Benvenuti S, MagroL, et al. Analysis of phenolic compounds andradical scavenging activity of Echinaceaspp[J]. J Pharm Biomed Anal.2004,35:289-301.
[109]李丽静,王继彦,王岩等.返魂草提取物及其有效成分抗病毒作用的研究[J].中国中医基础医学杂志.2005,11(8):585-587.
[110]王林青,张红英,崔保安等.金银花山银花绿原酸类提取物体外抗NDV作用研究[J].中国农学通报.2011,27(19):277-282.
[111]Chiang L C, Chiang W, Chang M Y, et al. Antiviral activity of Plantago majorextracts and related compounds in vitro[J]. Antiviral Res.2002,55:53-62.
[112]屈景年,莫运春,刘梦琴等.金银花中绿原酸一步提取法及绿原酸抗菌活性[J].化学世界.2005,3:167-169.
[113]梅林.秀山金银花叶茎中绿原酸的检测及其抑菌作用研究[J].中国药业.2007,16(3):5-7.
[114]王海燕,张仕华,赵谋明等.烟草绿原酸分离纯化及其抑菌性研究[J].现代食品科技.2008,24(3):233-237.
[115]Frank J, Kamal-Eldin A, RazAan A, et al. The dietary hydroxycinnamate caffeicacid and its conjugate chlorogenic acid increase vitamin E and cholesterolconcentrations in SpragueDawley rats[J]. J Argric Food Chem.2003,51:2526-2531.
[116]Shimoda H, Seki E, Aitani M. Inhibitory effect of green coffee bean extract onfat accumulation and body weight gain in mice[J]. BMC Complement AlternMed.2006,17(6):9.
[117]王强,陈东辉,邓文龙.金银花提取物对血脂与血糖的影响[J].中药药理与临床.2007,23(3):40-42.
[118]Chiang L C, Chiang W, Chang M Y, et al. Antileukemic activity of selectednatural products inTaiwan[J]. Am J Chin Med.2003,31:37-46.
[119]Bandyopadhyay G, Biswas T, RoyKC, et al. Chlorogenic acid inhibits Bcr-Abltyrosinekinase and triggers p38mitogen-activated protein kinase-dependentapoptosis in chronic myelogenous leukemic cells[J]. Blood.2004,104:2514-2522
[120]毛水春,顾谦群,崔承彬等.中药大血藤中酚类化学成分及其抗肿瘤活性[J].中国药物化学杂志.2004,14(6):326-330.
[121]古莹.绿原酸对白血病细胞的抑制作用及其作用机制的研究[D].浙江大学硕士毕业论文.2007:3-6.
[122]马力,唐凤敏,曾天舒等.菊花多糖和绿原酸免疫调节作用的研究[J].医药导报.2008,27(10):1168-1170
[123]Wang J，Mazza G. Effects of anthocyanins and other phenolic compounds on theproduction of tumor necrosis factor alpha in LPS/IFN-gamma-activatedRAW2647macrophages[J]. J Agric Food Chem.2002,50(15):4183-4189.
[124]Jin X H, Ohgam I K, Shiratorik, et al. Effects of blue honeysuckle(LoniceraaeruleaL.) extract onlipopolysaccharide-induced inflammationin vitro and in vivo[J]. Exp Eye Res.2006,82(5):860-867.
[125]Gong J, Chen S S. Polyphenolic antioxidants inhibit peptide presentation byantigen-presenting cells[J]. Int Immunopharmacol.2003,3:1841-1852.
[126]Wu H Z, Luo J, Yin Y X, et al. Effects of chlorogenic acid, an active compoundactivating calcineurin, purified from Flos Lonicerae on macrophage[J]. ActaPharmacol Sin.2004,25:1685-1689.
[127]刘玉敏.向日葵叶中绿原酸的提取及降血糖药效学研究[D].延吉:延边大学硕士论文，2006:4-6.
[128]Andrade-Cetto A, Wiedenfeld H. Hypoglycemic effect of Cecropiaobtusifolia-onstreptozoto in diabetic rats[J]. J Ethnopharmacol.2001,78:145-149.
[129]Krakauer T. The polyphenol chlorogenic acid inhibits staphylococcal exotoxininduced inflammatory cytokines and chemokines[J]. ImmunopharmacolImmunotoxicol.2002,24:113-119.
[130]Ina H, Yamada K, MatsumotoK, et al. Effects of benzyl glucoside andchlorogenic acid from Prunus mumeonadrenocortico tropic hormone (ACTH)and catecholamine levels in plasma of experimental menopausal model rats[J].Biol PharmBull.2004,27:136-137.
[131]Mueller E, Sarraf P, Tontonoz P, Evans RM, Martin KJ, Zhang M. et al.Terminal differentiation of human breast cancer through PPAR gamma [J]. MolCell.1998,1:465–470.
[132]Escher P, Wahli W. Peroxisome proliferator-activated receptors: insight intomultiple cellular functions [J]. Mutat Res.2000,448:121–138.
[133]Lazennec G, Canaple L, Saugy D, Wahli W. Activation of peroxisomeproliferator-activated receptors (PPARs) by their ligands and protein kinase Aactivators [J]. Mol Endocrinol.2000,14:1962–1975.
[134]Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphanreceptors to drug discovery [J]. J Med Chem.2000,43:527–550.
[135]Diep QN, Schiffrin EL. Increased expression of peroxisomeproliferator-activated receptor-alpha and-gamma in blood vessels ofspontaneously hypertensive rats [J]. Hypertension.2001,38:249-254.
[136]Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L. et al. Expression andfunction of PPARgamma in rat and human vascular smooth muscle cells [J].Circulation.2000,101:1311-1318.
[137]Park KS, Ciaraldi TP, Abrams-Carter L, Mudaliar S, Nikoulina SE, Henry RR.PPAR-gamma gene expression is elevated in skeletal muscle of obese and type IIdiabetic subjects [J]. Diabetes.1997,46:1230-1234.
[138]Rangwala SM, Lazar MA. Peroxisome proliferator-activated receptor gamma indiabetes and metabolism [J]. Trends Pharmacol Sci.2004,25:331–336.
[139]Sharma AM, Staels B. Review: peroxisome proliferator-activated receptorgamma and adipose tissue-understanding obesity-related changes in regulationof lipid and glucose metabolism [J]. J Clin Endocrinol Metab.2007,92:386-395.
[140]Fergus P McCarthy, Aoife C Delany, Louise C Kenny, Sarah K Walsh.PPAR-gamma possible drug target for complicated pregnancies[J]. BritishJournal of Pharmacology.2013,168:1074-1085.
[141]Debril MB, Renaud JP, Fajas L, et al. The pleiotropic functions of peroxisomeproliferator-activated receptor gamma [J].J Mol Med.2001,79:30-47.
[142]Fajas L, Debril MB, Auwerx J. Peroxisome proliferator-activatedreceptorgamma: from adipogenesis to carcinogenesis.J Mol Endocrino l2001;27:1–9.
[143]Desreumaux P, Dubuquoy L, Nutten S, et al. Attenuation of colon inflammationthrough activators of the retinoid X receptor (RXR)/peroxisomeproliferator-activated receptor gamma (PPARgamma) heterodimer. A basis fornew therapeutic strategies [J]. J Exp Med.2001,193:827-38.
[144]Marx N, Mach F, Sauty A, et al. Peroxisome proliferator-activatedreceptorgamma activators inhibit IFN-gamma-induced expression of the Tcell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells[J]. J Immunol.2000,164:6503-8.
[145]Harris SG, Phipps RP. The nuclear receptor PPAR gamma is expressed by mouseT lymphocytes and PPAR gamma agonists induce apoptosis [J]. Eur J Immunol.2001,31:1098-105.
[146]Hontecillas R, Wannemeulher MJ, Zimmerman DR, et al. Nutritional regulationof porcine bacterial-induced colitis by conjugated linoleicacid [J]. J Nutr.2002,132:2019-2027.
[147]Bassaganya-Riera J, Reynolds K, Martino-Catt S, et al. Activation of PPARgamma and delta by conjugated linoleic acid mediates protection fromexperimental inflammatory bowel disease [J]. Gastroenterology.2004,127:777-791.
[148]Alonso L, Cuesta EP, Gilliland SE. Production of free conjugated linoleic acidby Lactobacillus acidophilus and Lactobacillus casei of human intestinal origin[J]. J Dairy Sci.2003,86:1941-6
[149]Cuzzocrea S, Pisano B, Dugo L, et al. Rosiglitazone and15-deoxydelta12,14-prostaglandin J2, ligands of the peroxisome proliferator-activatedreceptor-gamma (PPAR-gamma), reduce ischaemia/reperfusion injury of the gut[J]. Br J Pharmacol.2003,140:366-76.
[150]Fitzgerald GA, Loll P. COX in a crystal ball: current status and future promise ofprostaglandin research [J]. J Clin Invest.2001,107:1335-7.
[151]Schopfer FJ, Lin Y, Baker PR, et al. Nitrolinoleic acid: an endogenousperoxisome proliferator-activated receptor gamma ligand [J]. Proc Natl Acad SciUSA.2005,102:2340-2345.
[152]Lewis JD, Lichtenstein GR, Stein RB, et al. An open-label trial of thePPARgamma ligand rosiglitazone for active ulcerative colitis [J]. Am JGastroenterol.2001,96:3323-3328.
[153]L Dubuquoy, C Rousseaux, X Thuru, L Peyrin-Biroulet, O Romano, P Chavatte,M Chamaillard, P Desreumaux. PPARc AS A NEW THERAPEUTIC TARGETIN INFLAMMATORY BOWEL DISEASES [J]. Gut.2006,55:1341-1349.
[154]E. Mor′an-Salvador, M. L′opez-Parra, V. Garc′a-Alonso et al. Role for PPARγin obesity-induced hepatic steatosis as determined by hepatocyte-andmacrophage-specific conditional knockouts [J]. FASEB Journal.2011,25(8):2538-2550.
[155]V. Gazit, J. Huang, A. Weymann, and D. A. Rudnick. Analysis of the role ofhepatic PPARγ expression during mouse liver regeneration [J]. Hepatology.2012,56(4):1489-1498.
[156]Z. Chen, P. A. Vigueira, N. Qi. et al. Insulin resistance and metabolicderangements in obese mice are ameliorated by a novel peroxisomeproliferator-activated receptor γ-sparing thiazolidinedione [J]. Journal ofBiological Chemistry.2012,287(28):23537-23548.
[157]Z.Han,T.Zhu,X.Liu. et al.15-deoxy-Δ12,14-prostaglandin J2reducesrecruitment of bone marrow-derived monocyte/macrophages in chronic liverinjury in mice [J]. Hepatology.2012,56(1):350–360.
[158]P. Escher, O. Braissant, S. Basu-Modak, L. Michalik, W. Wahli, B. Desvergne.Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting andrefeeding [J]. Endocrinology.2001,142(10):4195-4202.
[159]W. Su, C. R. Bush, B. M. Necela. et al. Differential expression, distribution, andfunction of PPAR-γ in the proximal and distal colon [J]. PhysiologicalGenomics.2007,30(3):342-353.
[160]G. D. Girnun, W. M. Smith, S. Drori et al. APC-dependent suppression of coloncarcinogenesis by PPARγ [J]. Proceedings of the National Academy ofSciences of the United States of America.2002,99(21):13771-13776.
[161]N. P.Evans, S. A. Misyak, E. M. Schmelz, A. J. Guri, R. Hontecillas, J.Bassaganya-Riera. Conjugated linoleic acid ameliorates inflammation-inducedcolorectal cancer in mice through activation of PPARγ [J]. Journal of Nutrition.2010,140(3):515-521.
[162]M. Adachi, R. Kurotani, K. Morimura et al. Peroxisome proliferator activatedreceptorγ in colonic epithelial cells protects against experimental inflammatorybowel disease [J]. Gut.2006,55(8):1104-1113.
[163]D. Kelly, J. I. Campbell, T. P. King. et al. Commensalanaerobic gut bacteriaattenuate inflammation by regulating nuclearcytoplasmic shutting of PPAR-γand ReIA [J]. Nature Immunology.2004,5(1):104-112.
[164]A. J. Guri, S. K. Mohapatra, W. T. Horne, R. Hontecillas, J. Bassaganya-Riera.The Role of T cell PPAR γin mice with experimental inflammatory boweldisease [J]. BMC Gastroenterology.2010,10:60.
[165]R.Hontecillas, W. T. Horne, M. Climent. et al. Immunoregulatory mechanismsof macrophage PPAR-γ in mice with experimental inflammatory bowel disease[J]. Mucosal Immunology.2011,4(3):304-313.
[166]R. Hontecillas, J. Bassaganya-Riera. Peroxisome proliferator-activated receptorγ is required for regulatory CD4+T cell-mediated protection against colitis [J].Journal of Immunology.2007,178(5):2940–2949.
[167]T. Breidert, J. Callebert, M. T. Heneka, G. Landreth, J. M. Launay, E. C. Hirsch.Protective action of the peroxisome proliferator-activated receptor-γ agonistpioglitazone in a mouse model of Parkinson’s disease [J]. Journal ofNeurochemistry.2002,82(3):615-624.
[168]T. Dehmer, M. T. Heneka, M. Sastre, J. Dichgans, J. B. Schulz. Protection bypioglitazone in the MPTP model of Parkinson’s disease correlates with IκBαinduction and block of NF κ B and iNOS activation [J]. Journal ofNeurochemistry.2004,88(2):494-501.
[169]F. Penas, G. A. Mirkin, E. Hovsepian et al.,“PPARγ ligand treatment inhibitscardiac inflammatory mediators induced by infection with different lethalitystrains of Trypanosoma cruzi [J]. Biochimica et Biophysica Acta.2013,1832(1):239-248.
[170]E. Hovsepian, G. A. Mirkin, F. Penas, A. Manzano, R. Bartrons, N. B. Goren.Modulation of inflammatory response and parasitism by15-Deoxy-Δ12,14prostaglandin J2in Tr ypanosoma cruzi-infected cardiomyocytes[J].International Journal for Parasitology.2011,41(5):553-562.
[171]A. Qu, Y. M. Shah, S. K. Manna, F. J. Gonzalez. Disruption of endothelialperoxisome proliferator-activated receptor γ accelerates diet-inducedatherogenesis in LDL receptor-null mice [J]. Arteriosclerosis, Thrombosis, andVascular Biolog.2012,32(1):65-73.
[172]A. T. Reddy, S. P. Lakshmi, J. M. Kleinhenz, R. L. Sutliff, C. M. Hart, R. C.Reddy. Endothelial cell peroxisome proliferator-activated receptorγ reducesendotoxemic pulmonary inflammation and injury [J]. Journal of Immunology.2012,189(11):5411-5420.
[173]B. Buitenhuis, C. M. R ntved, S. M. Edwards, K. L. Ingvartsen, P. S rensen. Indepth analysis of genes and pathways of the mammary gland involved in thepathogenesis of bovine Escherichia coli-mastitis [J]. BMC Genomics.2011,12:130.
[174]D. Yang, H. Yang, W. Li. et al. Generation of PPARγmonoallelic knockout pigsvia zinc-finger nucleases and nucleartransfer cloning [J]. Cell Research.2011,21(6):979-982.
[175]Stéphane Mandard, David Patsouris. Nuclear Control of the InflammatoryResponse in Mammals by Peroxisome Proliferator-Activated Receptors [J].PPAR Research.2013,(613864):1-23.
[176]Wang LH, Yang XY, Zhang X, Huang J, Hou J, Li J, Xiong H, Mihalic K, Zhu H,Xiao W, Farrar WL. Transcriptional inactivation of STAT3by PPARgammasuppresses IL-6-responsive multiple myeloma cells [J]. Immunity.2004,20:205-218.
[177]Nadiminty N, Lou W, Lee SO, Lin X, Trump DL, Gao AC. Stat3activation ofNF-{kappa}B p100processing involves CBP/p300-mediated acetylation [J].Proc Natl Acad Sci USA.2006,103:7264-7269.
[178]Wang LH, Yang XY, Zhang X, Farrar WL. Inhibition of adhesive interactionbetween multiple myeloma and bone marrow stromal cells by PPARgammacross talk with NF-kappaB and C/EBP [J]. Blood.2007,110:4373-4384.
[179]Jung WK, Park IS, Park SJ, Yea SS, Choi YH, Oh S, Park SG, Choi IW. The15-deoxyDelta12,14-prostaglandin J2inhibits LPS-stimulated AKT andNF-kappaB activation and suppresses interleukin-6in osteoblast-like cellsMC3T3E-1[J]. Life Sci.2009,85:46-53.
[180]Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, WillsonTM, Rosenfeld MG, Glass CK. A SUMOylation-dependent pathway mediatestransrepression of inflammatory response genes by PPAR-gamma [J]. Nature.2005,437:759-763.
[181]Chearwae W, Bright JJ. PPARgamma agonists inhibit growth and expansion ofCD133+brain tumour stem cells [J]. Br J Cancer.2008,99:2044-2053.
[182]Ide H, Nakagawa T, Terado Y, Kamiyama Y, Muto S, Horie S. Tyk2expressionand its signaling enhances the invasiveness of prostate cancer cells [J]. BiochemBiophys Res Commun.2008,369:292-296.
[183]Schuster C, Muller M, Freissmuth M, Sexl V, Stoiber D. Commentary on H. Ideet al. Tyk2expression and its signaling enhances the invasiveness of prostatecancer cells [J]. Biochem Biophys Res Commun.2008,366:869-870.
[184]Sen B, Saigal B, Parikh N, Gallick G, Johnson FM. Sustained Src inhibitionresults in signal transducer and activator of transcription3(STAT3) activationand cancer cell survival via altered Janus-activated kinase-STAT3binding [J].Cancer Res.2009,69:1958-1965.
[185]Wang Z, Sun Y. Targeting p53for Novel Anticancer Therapy [J]. Transl Oncol.2010,3:1-12.
[186]Bai MH, Ma HB, Wang XJ, Liu XX, Xue XH, Xue FJ. Effects of activatedPPARgamma on the expression of PTEN gene in pancreatic cancer cells [J].2008,24:717-720.
[187]Dong YW, Wang XP, Wu K. Suppression of pancreatic carcinoma growth byactivating peroxisome proliferator-activated receptor gamma involvesangiogenesis inhibition [J]. World J Gastroenterol.2009,15:441-448.
[188]Gregory T. Robbinsand Daotai Nie. PPARgamma, Bioactive Lipids, and CancerProgression [J]. Front Biosci.2012,17:1816-1834.
[189]KOKAI-KUN J F, CHANTURIYA T, MOND J J. Lysostaphin as a treatment forsystemic Staphylococcus aureus infection in a mouse model [J]. J AntimicrobChemoth,2007,60(5):1051-9.
[190]ZHENG J M, WATSON A D, KERR D E. Genome-wide expression analysis oflipopolysaccharide-induced mastitis in a mouse model [J]. Infection andimmunity,2006,74(3):1907-15.
[191]CHANDLER R L. Experimental bacterial mastitis in the mouse [J]. Journal ofmedical microbiology,1970,3(2):273-82.
[192]BROUILLETTE E, MALOUIN F. The pathogenesis and control ofStaphylococcus aureus-induced mastitis: study models in the mouse [J].Microbes and Infection,2005,7(3):560-8.
[193]NOTEBAERT S, MEYER E. Mouse models to study the pathogenesis andcontrol of bovine mastitis. A review [J]. Vet Quart,2006,28(1):2-13.
[194]BANNERMAN D D, PAAPE M J, HARE W R, et al. Increased levels ofLPS-binding protein in bovine blood and milk following bacteriallipopolysaccharide challenge [J]. J Dairy Sci,2003,86(10):3128-37.
[195]OVIEDO-BOYSO J, VALDEZ-ALARCON J J, CAJERO-JUAREZ M, et al.Innate immune response of bovine mammary gland to pathogenic bacteriaresponsible for mastitis [J]. J Infection,2007,54(4):399-409.
[196]BANNERMAN D D, PAAPE M J, HARE W R, et al. Increased levels ofLPS-binding protein in bovine blood and milk following bacteriallipopolysaccharide challenge [J]. J Dairy Sci,2003,86(10):3128-37.
[197]LEE J W, PAAPE M J, ELSASSER T H, et al. Elevated milk soluble CD14inbovine mammary glands challenged with Escherichia coli lipopolysaccharide [J].J Dairy Sci,2003,86(7):2382-9.
[198]Alain, K., Karrow, N.A., Thibault, C., St-Pierre, J., Lessard, M., Bissonnette, N.,Osteopontin: an early innate immune marker ofEscherichia coli mastitis harborsgenetic polymorphisms with possible links with resistance to mastitis [J]. BMCGenomics.2009,10.
[199]Gonen, E., Vallon-Eberhard, A., Elazar, S., Harmelin, A., Brenner, O.,Rosenshine, I., Jung, S., Shpigel, N.Y. Toll-like receptor4is needed to restrictthe invasion of Escherichia coliP4into mammary gland epithelial cells in amurine model of acute mastitis [J]. Cell. Microbiol.2007,9:2826–2838.
[200]Gu, B.B., Miao, J.F., Zhu, Y.M., Deng, Y.E., Zou, S.X. Protective effect ofretinoid against endotoxin-induced mastitis in rats [J]. Inflamm. Res.2009,58:81-88.
[201]Zhu, W., Gu, B., Miao, J., Lu, J., Zou, S.,. Dectin1activation ofbeta-(1–3)/(1–6)-Dglucan produces an anti-mastitis effect in rats [J]. Inflamm.Res.2011,60:937-945.
[202]Bannerman, D.D. Pathogen-dependent induction of cytokines and other solubleinflammatory mediators during intramammary infection of dairy cows [J]. J.Anim. Sci.2009,87:10-25.
[203]Zheng, J., Watson, A.D., Kerr, D.E. Genome-wide expression analysis oflipopolysaccharide-induced mastitis in a mouse model. Infect. Immun [J].2006,74:1907-1915.
[204]Giebelen, I.A., van Westerloo, D.J., LaRosa, G.J., de Vos, A.F., van der Poll, T.Local stimulation of alpha7cholinergic receptors inhibits LPS-induced TNFalpha release in the mouse lung [J]. Shock.2007,28:700-703.
[205]Medzhitov, R., Kagan, J.C. Phosphoinositide-mediated adaptor recruitmentcontrols toll-like receptor signaling [J]. Cell.2006,125:943-955.
[206]GU B B, MIAO J F, FA Y M, et al. Retinoic acid attenuateslipopolysaccharide-induced inflammatory responses by suppressingTLR4/NF-kappa B expression in rat mammary tissue [J]. Internationalimmunopharmacology,2010,10(7):799-805.
[207]CHU X, SONG K, XU K, et al. Ceftiofur attenuates lipopolysaccharide-inducedacute lung injury [J]. International immunopharmacology,2010,10(5):600-604.
[208]XINMIN D, YUNYOU D, CHAOSHENG P, et al. Dexamethasone treatmentattenuates early seawater instillation-induced acute lung injury in rabbits [J].Pharmacological research: the official journal of the Italian PharmacologicalSociety,2006,53(4):372-379.
[209]Hichem Lahouassa, Etienne Moussay, Pascal Rainard, et al. Differentialcytokine and chemokine responses of bovinemammary epithelial cells toStaphylococcus aureus and Escherichia coli [J]. Cytokine.2007,38:12–21.
[210]Dilip Pate,l RauclA Almeida, John R Dunlap,et al. Oliver. Bovine lactoferrinserves as a molecular bridge for internalization of Streptococcus uberis intobovine mammary epithelial cells [J]. Veterinary Microbiology,2009,137:297-301.
[211]MUN L, JUN M S, KIM Y M, et al.7,8-didehydrocimigenol from Cimicifugaerhizoma inhibits TNF-alpha-induced VCAM-1but not ICAM-1expressionthrough upregulation of PPAR-gamma in human endothelial cells [J]. Food andChemical Toxicology,2011,49(1):166-72.
[212]SHENG X Y, ZHANG Y B, GONG Z W, et al. Improved Insulin Resistance andLipid Metabolism by Cinnamon Extract through Activation of PeroxisomeProliferator-Activated Receptors [J]. Ppar Research,2008.
[213]JI Y Y, LIU J T, WANG Z D, et al. PPAR gamma agonist, rosiglitazone,regulates angiotensin II-induced vascular inflammation through theTLR4-dependent signaling pathway [J]. Lab Invest,2009,89(8):887-902.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |