丹参酮ⅡA对大鼠心脏纤维化的作用及机制

Effects of Tanshinone ⅡA on cardiac fibrosis in rats and its mechanisms

目的观察丹参酮ⅡA(TSNⅡA)能否抑制血管紧张素Ⅱ(AngⅡ)诱导的大鼠心肌纤维化;并初步探讨TSNⅡA抗纤维化作用是否与TSNⅡA下调转化生长因子-β1(TGF-β1)/Smads信号通路活性相关。方法 SD大鼠皮下植入渗透给药压力泵缓释AngⅡ,建立心脏纤维化模型。术后随机分为对照组、模型组、TSNⅡA低和高剂量组,每组8只。持续用药6周后,尾量法检测各组尾动脉压、左心室质量(LVW),并计算左心室质量指数(LVMI);Masson染色观察心脏纤维化情况;实时聚合酶链反应(Real-time PCR)检测结缔组织生长因子(CTGF)和纤溶酶原激活物抑制剂-1(PAI-1)m RNA表达水平;Western blot检测CTGF、PAI-1、TGF-β1和胞内信号蛋白Smad2/3的蛋白水平。结果 TSNⅡA对大鼠血压无明显影响,抑制AngⅡ诱导的胶原沉积,减少LVW和LVMI,下调CTGF、PAI-1、TGF-β1m RNA和蛋白表达,抑制TGF-β1蛋白表达及Smad2/3磷酸化水平,并呈浓度依赖性。结论 TSNⅡA可能通过下调TGF-β1/Smad2/3信号通路活性,有效抑制AngⅡ诱导的胶原沉积,CTGF、PAI-1过表达,改善大鼠心肌纤维化,发挥保护心脏的作用。

Objective To investigate the inhibitory effect of Tanshinone ⅡA（TSN ⅡA） on the angiotensinⅡ（Ang Ⅱ）-induced myocardial fibrosis in rats and its relationship with TGF-β1/Smads signaling pathway.Methods SD rat model of myocardial fibrosis was established by constant injection of Ang Ⅱ through a micropump. The rats were randomly divided into 4 groups after modeling including control group, model group,high-dose TSN Ⅱ group and low-dose TSN Ⅱ group with 8 rats in each group. Six weeks later, systolic blood pressure and left ventricular weight were measured and left ventricular mass index was worked out. Myocardial fibrosis was observed after Masson staining. The m RNA expression of connective tissue growth factor（CTGF） and plasminogen activator inhibitor 1（PAI-1） were detected by RT-PCR. Protein expressions of CTGF,PAI-1, TGF-β1and Smad2/3 in the ventricular tissue were detected by Western blot. Results Both high-dose and low-dose of TSN Ⅱ A failed to attenuate Ang Ⅱ-induced BP elevation but significantly attenuated the myocardial fibrosis. TSN Ⅱ down-regulated the expression of CTGF, PAI-1, TGF-β1and Smad2/3 induced by Ang Ⅱ. Conclusions TSN ⅡA attenuates myocardial fibrosis through down-regulation of TGF-β1/Smads signaling pathway and upregulation of CTGF and PAI-1.