丹参酮Ⅱ_A对AngⅡ诱导的心肌成纤维细胞增殖及Ⅰ型胶原合成的影响

目的:通过观察丹参酮ⅡA(TSN)对AngⅡ诱导的心肌成纤维细胞(CFs)增殖及Ⅰ型胶原合成的影响,探讨其抗心肌纤维化的作用机制。方法:差速贴壁法提取原代CFs,采用四氮唑盐(MTT)比色法测定细胞数目,ELISA法检测Ⅰ型胶原合成,RT-PCR法半定量检测Ⅰ胶原mRNA表达。结果:①AngⅡ组OD值高于空白对照组,两者比较有显著性差异(P<0.01);AngⅡ+TSN组OD值低于AngⅡ组,两者比较有显著性差异(P<0.01)。②AngⅡ组有促进心肌成纤维细胞分泌Ⅰ型胶原的作用,与空白对照组比较,有显著性差异(P<0.01);AngⅡ+TSN组Ⅰ型胶原含量低于AngⅡ组,两者比较,有显著性差异(P<0.01)。③AngⅡ组Ⅰ型胶原mRNA表达高于空白对照组,两者比较有显著性差异(P<0.05);AngⅡ+TSN组Ⅰ型胶原mRNA表达低于AngⅡ组,两者比较有显著性差异(P<0.05)。结论:AngⅡ可直接诱导CFs的增殖,促进其分泌Ⅰ型胶原,并能显著增加Ⅰ型胶原mRNA的表达;TSN对AngⅡ诱导的CFs增殖及Ⅰ型胶原分泌增加,及Ⅰ型胶原mRNA表达增强均有抑制作用。提示:TSN抗心肌纤维化作用的产生可能与丹参酮ⅡA抑制心脏局部的RAS系统有关。

Effects of Tanshinones Ⅱ_A on Proliferation and TypeⅠ Collagen Synthesis of Rat Cardiac Fibroblasts

Objective:To observe Tanshinones ⅡA on the proliferation and type Ⅰ collagen synthesis of rat cardiac fibroblasts that induced by AngⅡ,expecting to explore the mechanism of action of Tanshinones ⅡA in myocardial fibrosis.Methods:Isolated and cultured CFs of neonatal rats were used as experiment model.CFs proliferation or cell number was measured by MTT assay.Collagen Synthesis was measured by ELISA.TypeⅠcollagen mRNA expression was measured by RT-PCR.Results:All of A492 value of CFs by MTT assay,the secretion of type I collagen,and the mRNA expression of type Ⅰ collagen increased with AngⅡ were significantly higher than that of control group;decreased with AngⅡ+TSN were significantly lower than that of AngⅡ group.Conclusion:TSN can inhibit the proliferation,typeⅠcollagen synthesis and its mRNA expression in cultured rat CFs that increased with AngⅡ.This shows that the mechanism of action of TSN in myocardial fibrosis is probably related with inhibiting RAS system in regional heart.