Wnt-7a蛋白通过wnt/β-catenin通路抑制单侧输尿管梗阻小鼠肾脏上皮细胞-间充质细胞转分化

Wnt-7a Inhibites Epithelial to Mesenchymal Transition in Mice of Unilateral Ureteral Obstruction Model by Wnt/β-catenin Signaling Pathway

目的:观察Wnt-7a蛋白对单侧输尿管梗阻模型小鼠肾脏纤维化的拮抗作用及其可能机制。方法:雄性C57BL/6小鼠随机分为假手术组、UUO模型组和Wnt-7a蛋白治疗组,术后7 d行Masson染色观察肾间质纤维化程度,免疫组化染色检测肾组织E-钙黏素、α-平滑肌肌动蛋白、波形蛋白的表达,免疫印迹法测定肾皮质中E-钙黏素、α-平滑肌肌动蛋白及β-连环蛋白(β-catenin)的蛋白质表达。结果:与模型组相比,治疗组肾组织间质纤维化相对面积显著减少,α-平滑肌肌动蛋白及波形蛋白的表达显著减少,E-钙黏素表达显著增多(P<0.05)。同时,治疗组肾组织中β-catenin表达较模型组显著减少(P<0.05)。结论:Wnt-7a蛋白可以抑制肾脏上皮细胞-间充质细胞转分化的发生而减轻肾脏纤维化,其可能是通过抑制经典的wnt/β-catenin通路。

Objective：To investigate the protective effects of Wnt- 7a protein on renal interstitial fibrosis in mice of unilat- eral ureteral obstruction（UUO） model. Methods：Eighteen male C57BL/6 mice were randomly divided into 3 groups： sham -opera- tion group, the UUO model group and treatment group. All mice were sacrificed at the seventh day after the operation. Masson＇ s stain was performed as a main indicator of interstitial fibrosis. The expression of vimentin, a - smooth muscle actin, E - cadherin and β - catenin in renal tissue was detected by immunohistochemistry staining and Western - blot, respectively. Results： Compared with the UUO model group, the relative area of interstitial fibrosis in treatment group was reduced significantly （P 〈 0.05 ）. Furthermore, the expression of vimentin and a - SMA was significantly down - regulated （ P 〈 0.05 ） , and the expression of E - cadherin was signifi- cantly up - regulated （ P 〈 0.05 ）. The expression of 1β - catenin in treatment group was lower than that in the UUO model group. Condusion：Wnt-7a protein could decrease the interstitial fibrosis by inhibiting epithelial to mesenchymal transition in UUO mice, which may be through inhibiting the Wnt/13 - catenin signaling pathway.