氯沙坦对5/6肾切除大鼠残余肾组织中TGF-β1,p-Smad2/3及Smad7的作用

Effect of losartan on the expressions of TGF-β1,p-Smad2/3,and Smad7 in the remnant renal tissues of 5/6 nephrectomized rats

目的:观察氯沙坦对5/6肾切除大鼠肾组织中TGF-β1,p-Smad2/3及Smad7的影响,探讨氯沙坦抗肾小球硬化的作用机制。方法:雄性Wistar大鼠随机分为假手术组、模型组和氯沙坦治疗组,用两步法建立5/6肾切除模型,于术后12周处死各组大鼠。处死前留取24h尿检测尿蛋白,心脏取血检测血清肌酐、尿素氮,行HE和Masson染色观察各组大鼠肾组织病理改变,用免疫组织化学的方法检测肾组织中TGF-β1,p-Smad2/3及Smad7的表达。结果:模型组大鼠24h尿蛋白、血清肌酐、尿素氮和肾组织胶原相对面积明显较假手术组增多(P<0.01),氯沙坦治疗后上述指标均得到不同程度的改善。肾组织TGF-β1和p-Smad2/3在假手术组低表达,模型组呈强阳性表达,而氯沙坦治疗组TGF-β1和p-Smad2/3表达较模型组明显减弱(P<0.01)。假手术组肾组织可见较多的Smad7表达,模型组其表达明显减弱(P<0.01),而氯沙坦治疗后Smad7表达较模型组增强(P<0.01)。结论:氯沙坦可以通过影响5/6肾切除大鼠肾组织中TGF-β/Smads信号通路中TGF-β1,p-Smad2/3和Smad7的表达而起到抗肾小球硬化的作用。

Objective To investigate the mechanism of losartan treating glomerulosclerosis and to observe the effect of losartan on the expressions of TGF-β1,p-Smad2/3,and Smad7 in the renal tissues of 5/6 nephrectomized rats.Methods Male Wistar rats were randomly divided into a sham-operated group,a 5/6 nephrectomized model group,and a losartan treated group.The rats in the model group and the losartan treated group were performed 5/6 nephrectomy by the method with 2 procedures.Twelve weeks after of the operation,all rats were killed.The 24-hour urinary protein,serum creatinine,and urea nitrogen were detected.Pathological changes of the renal tissues were observed by HE and Masson staining,and the expressions of TGF-β1,p-Smad2/3,and Smad7 were detected by immunohistochemical staining.Results The 24-hour urinary protein,serum creatinine,urea nitrogen,and the relative area of collagen in the renal tissues of the rats in the model group significantly increased（P〈0.01）,and losartan could reduce these indexes.The expressions of TGF-β1 and p-Smad2/3 were just at a low level in the renal tissues of the rats in the sham-operated group,and were strongly positive in the model group;but losartan could decrease the expressions of TGF-β1 and p-Smad2/3（P〈0.01）.The expression of Smad7 in the model group was fewer than that in the sham-operated group（P〈0.01）,but losartan could improve the expression of Smad7（P〈0.01）.Conclusion Losartan may implement its anti-glomerulosclerosis by affecting TGF-β1,p-Smad2/3,and Smad7 of TGF-β/Smads pathway of the renal tissues of 5/6 nephrectomized rats.