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JAK2/STAT3信号通路在白藜芦醇抗肝脏缺血再灌注损伤中的作用及机制研究
Role of Janus Kinase 2/signal Transducer and Activator of Transcription 3 Signaling Pathway in Attenuation of Hepatic Ischemia-reperfusion Injury by Resveratrol in Rats
【摘要】 目的:探讨JAK2/STAT 3信号通路在白藜芦醇抗肝脏缺血再灌注损伤中的作用及机制。方法:健康雄性SD大鼠40只随机分为4组,假手术对照(SC)组、肝脏缺血再灌注(HIR)组、白藜芦醇处理(Res+HIR)组、JAK2/STAT 3通路阻断剂AG490(Res+AG490+HIR)组。建立急性肝脏缺血再灌注损伤模型,于再灌注6h后收集动物血液和肝脏标本。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和碱性磷酸酶(AKP)及炎症因子IL-6、TNF-α、IL-10、TGF-β的变化。肝脏组织HE染色,光镜下观察肝组织形态学变化。结果:与HIR组相比,Res+HIR组大鼠肝组织病理学变化明显改善,血清中反映肝脏功能学的指标ALT、AST及AKP的浓度明显降低,同时血清中抗炎因子IL-10和TGF-β含量升高,而促炎因子IL-6和TNF-α含量降低;使用JAK2/STAT 3通路阻断剂AG490后,肝组织病理学改变明显,ALT、AST及AKP的浓度明显升高,IL-10和TGF-β含量降低,而IL-6和TNF-α含量明显升高。结论:白藜芦醇对肝脏缺血再灌注损伤的保护作用可能是通过激活JAK2/STAT 3信号通路,改变再灌注过程中炎性反应实现的。
【Abstract】 Objective:To investigate whether the janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT 3)signaling pathway is involved in anti-hepatic ischemia-reperfusion injury of resveratrol in rat.Methods:40healthy male Sprague-Dawley(SD)rats were randomly divided into 4groups:sham control(SC)group,hepatic ischemia-reperfusion injury(HIR)group,resveratrol(Res+HIR)group,JAK2/STAT 3inhibitor AG490(Res+AG490+HIR)group.The blood sample and liver tissue samples were collected 6hours after reperfusion.The pathological changes of the liver were observed.Serum ALT,AST and AKP activity were detected as indicators of liver function damage and the content of TNF-α,IL-6,IL-10 and TGF-βin serum were detected by ELISA.Results:Compared with the HIR group,the pathological injury of the liver was significantly improved and the concentrations of serum AST,ALT and AKP was significantly lower in Res+HIR group(P<0.01).Meanwhile,the release of proinflammatory cytokine including TNF-αand IL-6was significantly lower and the release of antiinflammatory cytokine including IL-10 and TGF-βwas evidently enhanced.After addition of JAK2/STAT 3inhibitor AG490,the pathological damaged of the liver was evidently observed and the concentrations of serum AST,ALT and AKP was significantly enhanced in Res+HIR group(P<0.01),while the TNF-αand IL-6was significantly enhanced and the antiinflammatory cytokine including IL-10 and TGF-βwas evidently lower in Res+AG490+HIR group(P<0.01).Conclusion:The results show that resveratrol could protect the hepatic ischemia reperfusion injury by reducing the inflammatory response through the JAK2/STAT 3signaling.
【Key words】 resveratrol; inflammatory cytokine; janus kinase 2/signal transducer and activator of transcription 3 signaling pathway;
- 【文献出处】 长治医学院学报 ,Journal of Changzhi Medical College , 编辑部邮箱 ,2016年06期
- 【分类号】R575
- 【被引频次】2
- 【下载频次】147