五味子乙素抗肾纤维化作用及机制研究

Protective effect of Schisandrin B on renal fibrosis and underlying mechanism

目的探讨五味子乙素对肾纤维化的改善作用及其机制。方法以分别不同剂量的五味子乙素给缺血再灌注(I/R)模型小鼠灌胃。通过Masson染色对各组小鼠肾纤维化进行评价,免疫组织化学染色检测各组小鼠肾组织α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原蛋白(CollagenⅠ)的表达;Western blot法检测各组小鼠肾组织α-SMA、CollagenⅠ、上皮性钙粘蛋白(E-cadherin)、转化生长因子β1(TGF-β1)和p-Smad3的表达水平。结果 Masson染色结果显示,五味子乙素治疗组较I/R组小鼠肾间质纤维化及小管萎缩减轻;免疫组织化学染色结果显示,治疗组较I/R组α-SMA和CollagenⅠ蛋白表达减少;Western blot检测结果显示,治疗组较I/R组E-cadherin表达增高,α-SMA、CollagenⅠ、TGF-β1和p-Smad3表达均下降,且呈现出剂量效应。结论五味子乙素具有抗肾纤维化的作用,其机制可能与抑制TGF-β/Smad信号通路有关,提示五味子乙素有望成为抗肾纤维化的临床治疗药物。

Objective To investigate the protective of Schisandrin （Sch B） on renal fibrosis and underlying mechanism. Methods Mice were subjected to ischemia-reperfusion （I/R） injury in presence or absence of Sch B. Masson staining was performed for morphological grading of renal fibrosis. α-SMA and Collagen I expression in kidney tissue were determined by Immunohistochemistry. The expression levels of α-SMA, collagenⅠ, E-cadherin, transforming growth factor 1 （TGF-β1） and p-Smad3 were measured by Western blot. Results Renal fibrosis and tubular atrophy were significantly alleviated by Sch B treatment when compared with I/R group. Immunohistochemistry staining showed that α-SMA and Collagen I in the I/R group increased significantly, which was attenuated by Sch B. Western blot suggested that, in the Sch B group, the expression of E-cadherin was increased while α-SMA, Collagen I, TGF-β1 and p-Smad3 decreased dramatically in a dose dependent manner in comparison with those in the I/R group. Conclusions Data confirms that SchB can ameliorate renal fibrosis by inhibiting TGF-β/Smad signaling pathway, which could be a potential therapeutic intervention for renal fibrosis.