苯那普利干预Wnt信号通路抑制UUO大鼠肾纤维化的实验研究

目的: 探讨苯那普利对肾纤维化的拮抗作用。方法: 将54只SD大鼠随机分为3组：假手术组、模型组、苯那普利组，除假手术组外，其他各组均采用单侧输尿管结扎手术方法建立大鼠肾纤维化模型，取手术侧肾组织做病理检测，Masson染色观察其病理变化，冰冻切片免疫荧光染色检测转化生长因子-β1（TGF-β1）、IV 型胶原蛋白（Col-IV）、 Wnt1、Wnt4在肾组织的阳性染色表达。实时荧光定量 PCR检测TGF-β1、Col-IV、Wnt1、Wnt4的mRNA 在肾组织中的表达情况。结果: Masson染色显示：与假手术组比较，各造模组胶原纤维蓝染部分明显增多、肾纤维化程度显著增加；与模型组比较，苯那普利组胶原纤维蓝染部分明显减少、肾纤维化程度相对减少。免疫组化和PCR结果显示：与模型组相比，苯那普利组Wnt1、Wnt4、TGF-β1、Col-IV阳性表达及mRNA表达显著下降。结论: 苯那普利能通过降低TGF-β1、Col-IV、Wnt1、Wnt4的表达，有效降低肾纤维化水平，从而达到改善肾纤维化的作用。

Experimental study of benazepril intervene Wnt signaling inhibits renal fibrosis in UUO rats

AIM: To investigate the antagonism mechanism of benazepril on renal fibrosis of unilateral uretreal obstructire(UUO). METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three groups: sham operation group, model group, benazepril group. All the other groups were treated with surgery method of unilateral ureteral ligation to establish a rat model of renal fibrosis except the sham operation group. The pathological changes were observed by Masson staining; the positive staining expression of TGF-beta1, Col-IV, Wnt1, Wnt4 in frozen sections were observed by immunofluorescence staining; the expressions TGF-beta1, Col-IV, Wnt1and Wnt4 mRNA in renal tissues were detected by real time fluorescence quantitative PCR. RESULTS: Masson staining results: compared with the sham group, the parts of blue dye collagen fiber and the degree of renal fibrosis increased significantly in all modeled groups; compared with the model group, the parts of blue dye collagen fiber and the degree of renal fibrosis decreased significantly in benazepril group. Immunofluorescence and PCR results: compared with the model group, the positive expression of Wnt1, Wnt4, TGF-beta1, Col - IV and mRNA in the benazepril group decreased significantly. CONCLUSION: Benazepril can improve renal fibrosis by inhibiting the expression of TGF-beta1, Col-V, Wnt1, Wnt4 and ameliorating the level of renal fibrosis.