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

摘要:

目的  观察丹参酮ⅡA（TSN ⅡA）能否抑制血管紧张素Ⅱ（Ang Ⅱ）诱导的大鼠心肌纤维化；并初步探讨TSN ⅡA抗纤维化作用是否与TSN ⅡA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Ang Ⅱ，建立心脏纤维化模型。术后随机分为对照组、模型组、TSN ⅡA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）mRNA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  TSN ⅡA对大鼠血压无明显影响，抑制Ang Ⅱ诱导的胶原沉积，减少LVW和LVMI，下调CTGF、PAI-1、TGF-β1 mRNA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  TSN ⅡA可能通过下调TGF-β1/Smad2/3信号通路活性，有效抑制Ang Ⅱ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。

Abstract:

Objective To investigate the inhibitory effect of Tanshinone ⅡA (TSN ⅡA) on the angiotensin Ⅱ (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. Myo-cardial fibrosis was observed after Masson staining. The mRNA 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-β1 and Smad2/3 in the ventricular tissue were detected by Western blot. Results Both high-dose and low-dose of TSN ⅡA 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-β1 and 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.