辛伐他汀减轻UUO大鼠肾纤维化及可能机制的研究

Study on simvastatin improving the UUO rats renal fibrosis and anti-fibrosis plausible mechanism

目的本研究旨在探讨辛伐他汀改善输尿管梗阻(UUO)大鼠肾组织纤维化以及可能的机制。方法 30只SD大鼠,随机分为假手术对照组(Sham组)、模型组(UUO组)和辛伐他汀治疗组(Sim组),治疗组术前3 d予20 mg·kg^(-1)·d^(-1)辛伐他汀生理盐水混悬液3 mL灌胃治疗,对照组及模型组予等体积生理盐水灌胃。成模后7 d处死各组大鼠。行HE、Masson、PAS染色方法光镜下观察大鼠肾脏病理改变;免疫组化观察Wnt4和β-catenin蛋白在肾组织的表达; Western blotting检测各组大鼠肾皮质β-catenin、Wnt4、GSK-3β、p-GSK-3β、CollagenⅠ、α-SMA和E-cadherin蛋白在各组大鼠肾组织的相对表达量。结果与Sham组相比,UUO组大鼠肾组织纤维化病变明显,肾组织β-catenin、Wnt4、α-SMA、p-GSK-3β、CollagenⅠ蛋白的表达明显增多(P <0.05),E-cadherin蛋白表达减少(P <0.01),与UUO组相比,Sim组肾组织α-SMA、CollagenⅠ、Wnt4、β-catenin和p-GSK-3β蛋白表达减少(P <0.05),E-cadherin蛋白表达多(P <0.05)。结论辛伐他汀能改善肾脏纤维化病变,可能与其抑制Wnt4/β-catenin信号通路的激活和传导有关。

Objective This study is aim to investigate simvastatin reducing the renal tissue fibrosis and the possible mechanism in unilateral ureteral obstruction( UUO) rats. Methods The 30 Sprague-Dawley( SD) rats were divided randomly into 3 groups: the sham group( Sham),the model group( UUO) and the simvastatin group( Sim). The simvastatin group had been treated with 3 mL the suspension of normal saline and Simrvastatin( 20 mg/kg/d) by daily gastric gavage,from three days before the UUO operation to the day of has been sacrificed,the Sham and model group were treated with the same dose normal saline in an identical fashion. each group were sacrificed respectively at 7 days after surgery. Using HE,PAS and Masson staining to observe the pathological changes in renal tissue. In addition,immunohistochemistry st-aining were employed to detect the expression of Wnt4 and β-catenin protein in renal tissue. And Western blotting were used to detect the expression of Wnt4,β-catenin,G-SK-3β、p-GSK-3β、E-cadherin,α-SMA and collagenⅠprotein in the rats renal tissue. Results Compared with the sham group,the typical morphologic changes were presenting in the model group,the expression of Wnt4,β-catenin,α-SMA,p-GSK-3β and collagenⅠ protein was increased significantly( P < 0.05),while the levels of Ecadherin protein was obvious decreased( P < 0.01). Compared with the model group,the renal fibrosis were obviously relief in the simvastatin group, accompanied by the levels of Wnt4,β-catenin,p-GSK-3β, α-SMA and collagen Ⅰ protein expression was obvious decreased( P < 0.05),and the expression of Ecadherin protein was evident increased( P <0.05). Conclusions The simvastatin reduces the renal fibrosis in UUO rats,the possible mechanism,maybe relate to inhibiting the the activation and transduction of Wnt4/β-catenin signaling pathway.