抑制JAK/STAT3信号通路对重症急性胰腺炎肾损伤的保护作用  

Inhibition of the JAK/STAT3 signaling pathway reduces acute renal injury in rats with experimental severe acute pancreatitis

作　　者：李敏利[1] 张晓华[1] 朱人敏[1] 杨妙芳[1] 王斌[1] 

机构地区：[1]中国人民解放军南京军区总医院干部消化内科,江苏省南京市210002

出　　处：《世界华人消化杂志》2011年第32期3297-3301,共5页World Chinese Journal of Digestology

基　　金：中国人民解放军南京军区南京总医院科研基金资助项目;No.2009020~~

摘　　要：目的:探讨抑制JAK/STAT3信号通路对重症急性胰腺炎(severe acute pancreatitis,SAP)肾损伤作用的实验研究.方法:♂SD大鼠(n=56)随机分为3组:对照组、SAP造模组和JAK抑制剂-AG490治疗组.以4%牛磺胆酸钠胰胆管逆行注射诱导大鼠SAP模型.动态检测血清淀粉酶(AMY)、肌酐(Cr)、尿素氮(BUN)水平;ELISA法检测血清IL-6及TNF-α表达情况;光镜下观察胰腺及肾脏病理变化;Western blotting法检测STAT3及p-STAT3在肾脏中蛋白表达水平.结果:与正常对照组比较,SAP各组胰腺和肾脏病理损伤程度随病情进展逐渐加重,AMY、Cr、BUN水平均明显升高(P<0.01),IL-6及TNF-α表达水平显著上调(P<0.01),STAT3及p-STAT3表达明显增加,且18 h后达高峰;AG490处理后,上述各指标与SAP各组同时间点均显著降低(P<0.01),AG490治疗组病理损伤改善程度优于SAP组.结论:JAK/STAT3信号通路参与了SAP肾损伤的病理过程,抑制JAK/STAT3可以明显抑制STAT3的过度激活,有效减轻大鼠SAP时的炎症反应和肾损伤.AIM：To investigate whether inhibition of the JAK/STAT3 signaling pathway exerts a protective effect against acute renal injury in rats with experimental severe acute pancreatitis（SAP） and to explore the potential mechanisms involved. METHODS：Fifty-six male SD rats were randomly divided into three groups：control group, SAP group and JAK inhibitor（AG490）-treated group.A rat model of SAP was reproduced by retrograde infusion of 4%sodium taurocholate into the biliopancreatic duct.The levels of serum amylase（AMY）,creatinine（Cr） and urea nitrogen （BUN） were measured.The concentrations of IL-6 and TNF-αwere determined by ELISA. Pathological changes in the pancreas and kidney were evaluated.The expression of STAT3 and p-STAT3 in the kidney was determined by Western blotting. RESULTS：Compared to the normal control group,pancreatic and renal injuries were gradually aggravated with disease progression,and serum levels of IL-6,TNF-αAMY,Cr and BUN and expression of STAT3 and p-STAT3 increased significantly（all P 0.01） in the SAP group.In the AG490-treated group,all the above parameters improved significantly in comparison with those in the SAP model group（all P 0.01）. CONCLUSION：The JAK/STAT3 signaling pathway is involved in the development of renal injury in rats with SAP,and inhibition of this pathway can significantly inhibit excessive STAT3 activation,which may in turn effectively reduce renal injury.

关 键 词：信号转导子和转录活化子3 重症急性胰腺炎 肾损伤 细胞因子 

分 类 号：R576[医药卫生—消化系统]