Ouyang Jingfeng, Gao Zuming, Ren Zihua, Hong Dongsheng, Qiao Hongxiang, Chen Yan
College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
Pharmazie. 2010 Aug;65(8):607-13.
Rat mesenchymal stem cells (rMSCs) and salidroside have been applied in the treatment of hepatic fibrosis. The present study aimed to investigate the mechanism of hepatic differentiation of rMSCs in vitro and synergistic effects of rMSCs and salidroside on the experimental hepatic fibrosis in rats. rMSCs treated with 10 microg/mL, 20 microg/mL and 50 microg/mL salidroside were taken at 14 days and the proteins were subjected to western blot analysis. Hepatic fibrosis was induced in rats by administration of porcine serum for 8 weeks. Then, rats were randomly divided into 6 groups: control group, hepatic fibrosis group (model), salidroside group, rMSCs group and rMSCs plus salidroside group. Four weeks later, the localization and differentiation of rMSCs were determined. To evaluate the improvement of liver injury, the pathology of hepatocytes (or liver) and serum transforming growth factor-beta1 (TGF-beta1) were assessed. Induced rMSCs expressed alpha-fetoprotein (AFP) and albumin (ALB), which suggested rMSCs differentiated towards hepatocytes; moreover, E-adherin and beta-catenin were involved in the hepatic differentiation of rMSCs. In experiments of rMSCs transplantation, the amount of collagen in the liver of rMSCs plus salidroside treated rats was significantly lowered accompanied by reduced expression of TGF-beta1, when compared to the control group and rMSCs group. These findings suggested the synergistic effects of rMSCs transplantation and salidroside on hepatic fibrosis. Salidroside could differentiate rMSCs towards hepatocytes and E-adherin and beta-catenin were involved in the hepatic differentiation of rMSCs. Treatment with rMSCs transplantation and salidroside exerted synergistic effects on the experimental hepatic fibrosis via suppressing the expression of TGF-beta1.
大鼠间充质干细胞(rMSCs)和红景天苷已应用于肝纤维化的治疗。本研究旨在探讨rMSCs体外向肝细胞分化的机制以及rMSCs与红景天苷对大鼠实验性肝纤维化的协同作用。在第14天采集用10微克/毫升、20微克/毫升和50微克/毫升红景天苷处理的rMSCs,并对蛋白质进行蛋白质印迹分析。通过给予猪血清8周诱导大鼠肝纤维化。然后,将大鼠随机分为6组:对照组、肝纤维化组(模型组)、红景天苷组、rMSCs组和rMSCs加红景天苷组。4周后,确定rMSCs的定位和分化。为了评估肝损伤的改善情况,评估肝细胞(或肝脏)的病理学和血清转化生长因子-β1(TGF-β1)。诱导的rMSCs表达甲胎蛋白(AFP)和白蛋白(ALB),这表明rMSCs向肝细胞分化;此外,E-钙黏蛋白和β-连环蛋白参与rMSCs的肝分化。在rMSCs移植实验中,与对照组和rMSCs组相比,rMSCs加红景天苷处理的大鼠肝脏中的胶原量显著降低,同时TGF-β1的表达减少。这些发现提示rMSCs移植和红景天苷对肝纤维化有协同作用。红景天苷可使rMSCs向肝细胞分化,E-钙黏蛋白和β-连环蛋白参与rMSCs的肝分化。rMSCs移植和红景天苷治疗通过抑制TGF-β1的表达对实验性肝纤维化发挥协同作用。