摘要
目的探讨蛋白酪氨酸激酶2/信号传导与转录激活因子3(JAK2/STAT3)信号通路在大鼠肾脏移植慢性排斥反应中的作用机制。方法将60只大鼠分为空白对照组[供鼠(10只)、受鼠(10只)均为Lewis大鼠]、阳性对照组[供鼠(10只)为F344大鼠,受鼠(10只)为Lewis大鼠]和STAT3拮抗组[供鼠(10只)为F344大鼠,受鼠(10只)为Lewis大鼠],检测其术前及术后12周血肌酐(SCr)及尿素氮(BUN)水平并进行比较。比较3组大鼠肾脏组织病理学变化和慢性移植损伤指数(CADI)评分。采用免疫组化检测转化生长因子(TGF)-β1/果蝇母性DPP同源蛋白(Smad)3、α平滑肌肌动蛋白(α-SMA)纤维化指标。采用蛋白质印记法(Western blot)检测TGF-β1、α-SMA、JAK2和STAT3蛋白的表达。结果空白对照组和STAT3拮抗组大鼠血清SCr及BUN水平均低于阳性对照组(P<0.05)。阳性对照组大鼠肾脏组织弥漫性炎症细胞浸润表现较明显,其他两组大鼠中炎症细胞浸润较少。阳性对照组大鼠CADI评分明显高于其他两组(P<0.05)。空白对照组和STAT3拮抗组大鼠肾脏组织中TGF-β1、α-SMA、JAK2和STAT3蛋白表达水平明显低于阳性对照组(P<0.05)。结论STAT3的特异性抑制剂可在大鼠肾脏移植慢性排斥反应中抑制JAK2/Smad3信号通路所引起的炎症反应,对肾脏移植起到一定的保护作用。
Objective To explore the mechanism of Janus family of tyrosine kinases 2/signal transduction and transcription activator 3(JAK2/STAT3)signaling pathway in chronic rejection of kidney transplantation in rats.Methods Sixty rats were divided into blank control group(the 10 donor and 10 recipient rats were all Lewis rats),positive control group(10 donor rats were F344 rats,10 recipient rats were Lewis rats)and STAT3 antagonistic group(10 donor rats were F344 rats,10 recipient rats were Lewis rats).The levels of serum creatinine(SCr)and blood urea nitrogen(BUN)were measured and compared before and 12 weeks after operation.The renal histopathological changes and chronic allograft damage index(CADI)scores of the 3 groups were compared.TGF-β1/Smad3 andα-smooth muscle actin(α-SMA)fibrosis index were detected by immunohistochemistry.The expression of TGF-β1,α-SMA,JAK2 and STAT3 protein were detected by Western blotting.Results The serum levels of SCr and BUN in the blank control group and STAT3 antagonistic group were lower than those in the positive control group(P<0.05).In the positive control group,diffuse inflammatory cell infiltration was more obvious,while the inflammatory cell infiltration were less in the other 2 groups.The CADI scores in the positive control group were significantly higher than those in the other 2 groups.The expression levels of TGF-β1,α-SMA,JAK2 and STAT3 protein in the kidney of rats in the blank control group and STAT3 antagonistic group were significantly lower than those in the positive control group(P<0.05).Conclusion STAT3 specific inhibitors can inhibit the inflammatory response induced by JAK2/Smad3 signaling pathway in the chronic rejection of renal transplantation,and play a protective role in renal transplantation.
作者
蒋欣
曲青山
房军
梁韶峰
孙东
Jiang Xin;Qu Qingshan;Fang Jun;Liang Shaofeng;Sun Dong(Department of Organ Transplantation,Zhengzhou People’s Hospital,Zhengzhou 450000 China)
出处
《临床内科杂志》
CAS
2020年第6期440-443,共4页
Journal of Clinical Internal Medicine
基金
河南省医学科技攻关计划项目(2018020823)。
关键词
蛋白酪氨酸激酶2/信号传导与转录激活因子3信号通路
肾脏移植
慢性排斥反应
Janus family of tyrosine kinases 2/signal transduction and transcription activator 3 signaling pathway
Kidney transplantation
Chronic rejection
