黄芪三萜皂苷通过抑制TGF-β1/Smad2、p38MAPK信号抑制CVB3诱导的心肌纤维化

Astragalus triterpenoid saponins attenuated CVB3-induced cardiac fibrosis via suppressed TGF-β1/Smad2,p38MAPK signal pathway

目的本文旨在研究黄芪三萜皂苷(astragalus saponins,AST)对CVB3诱导心肌纤维化的保护作用及机制。方法使用CVB3病毒和BALB/c小鼠制备病毒性心肌炎模型并使用AST进行干预。记录不同处理组小鼠的生存曲线、检测不同干预组小鼠外周血中CK-MB水平、心肌组织HE染色和天狼星红染色检测心肌损伤和纤维化水平及通过western blot和qPCR检测心肌组织中TGF-β1、Smad2及p38MAPK水平以研究AST的作用机制。结果 AST能够显著提高小鼠的生存率,显著降低CVB3诱导的心肌损伤和外周血中CK-MB水平。与CVB3组小鼠比较,AST干预组小鼠心肌组织纤维化面积显著减少。无论是RNA水平还是蛋白水平,CVB3能够显著诱导TGF-β1、Smad2及p38MAPK在心肌组织中的表达,而AST对此具有显著地抑制作用。结论 AST对CVB3诱导的心肌组织纤维化具有显著地抑制作用,这种保护作用与抑制CVB3诱导的TGF-β1/Smad2、p38MAPK信号在心肌组织中的活化有关。

Objective To determine the protective effect and mechanism of Astragalus saponins(AST) on CVB3-induced cardiac fibrosis.Methods BALB/c mice and CVB3 were used to prepare virus myocarditis model and treated with AST. Recording mouse survival rate, arraying CKMB level in plasma were performed to assess the protective effect of AST on CVB3-induced virus myocarditis. The degree of collagen deposition was evaluated by picrosirius red(PSR) staining and images were analysed using a quantitative digital image analysis system(Image-Pro Plus 6.0). Protein level and mRNA level of TGF-β1, Smad2, p38 MAPK were detected by western blot and qPCR to study the protective effect of AST on CVB3-induced cardiac fibrosis. Results AST could significantly improve mouse survival rate and decrease CVB3-induced myocardial damage. CK-MB level was significantly decreased in plasma of AST treated mice comparing with CVB3-induced mice. Comparing with normal mice, heart fibrosis area was significantly increased in heart of CVB3-induced mice, while those were significantly inhabited in heart of AST treated mice. In the heart of CVB3-induced mice, TGF-β1, Smad2, p38 MAPK mRNA level and protein level were significantly increased, while those were inhabited in heart of AST treated mice. Conclusions Our results support that AST could protect heart from CVB3-induced virus myocarditis via inhabiting cardiac fibrosis via attenuating TGF-β1/Smad2, p38 MAPK signal pathway in heart.