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

摘要:

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。

Abstract:

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.