脂多糖诱导的急性肾损伤小鼠模型肾脏中JNK信号通路的激活

Activation of JNK signal pathway in kidney of mice with lipopolysaccharide induced acute kidney injury

目的探讨JNK信号通路激活在脂多糖(LPS)诱导的急性肾损伤(AKI)发病中的作用。方法 48只小鼠随机分为对照组和AKI组,分别检测血清尿素氮、肌酐以及胱抑素C,HE染色观察肾组织病理改变,免疫组化、Western blot检测肾组织p-JNK和p-c-Jun蛋白表达部位及强度,ELISA检测血中肿瘤坏死因子-α(TNF-α)及白介素1β(IL-1β)水平。结果小鼠腹腔注射LPS后,血清尿素氮、肌酐、胱抑素C均较对照组均明显升高,肾组织病理损伤呈进行性加重。正常小鼠各时间点可见p-JNK和p-c-Jun在肾小管、肾小球系膜区有微量表达。AKI组小鼠p-JNK及p-c-Jun在肾小管等部位大量表达。与对照组相比,AKI组p-JNK和p-c-Jun蛋白水平在1 h后即开始升高,以造模4 h时增高最明显,30 h时逐渐下降。与之相应,血中TNF-α和IL-1β水平亦明显升高,于4 h达峰值后逐渐下降。结论 JNK信号通路激活在LPS诱导的AKI发病中起重要作用,JNK信号通路活化后可诱发TNF-α和IL-1β等炎性因子的表达,继而介导AKI的发生和发展。

Objective To explore the activation and its role of JNK signal pathway in kidney of mice with lipopolysaccharide （LPS） induced acute kidney injury （AKI）.Methods Forty-eight male mice were randomly divided into control group and AKI group measure the level of blood urea nitrogen （BUN） 、serum creatinine （Scr） and cystatin C（Cys C）respectively.The pathologic change of the kidney was detected by HE.Immunohistochemistry （IHC） and Western blot were applied to detect the expression of p-JNK and p-c-Jun respectively.Serum level of TNF-α and IL-1β was determined by ELISA.Results Compared with the control group,BUN,Scr and Cys C levels of the AKI group rose considerably after the injection and the pathological damages of their renal tissues showed a continual worsening trend.A weak expression of p-JNK and p-c-Jun on the renal tubule and glomerular mesangial region was detected.The expression of protein increased remarkably at 4 hours but decreased gradually at 30 hours.Meanwhile,TNF-α and IL-1β levels in the blood also rose obviously and peaked at 4 hours after the injection followed by a gradual decrease.Conclusions JNK signal pathway may play an important role in the pathogenesis of AKI induced by LPS.Activation of JNK signal pathway could mediate the occurrence and development of AKI by triggering the expression of TNF-α and IL-11β.