麝香保心丸对压力超负荷大鼠心肌纤维化的影响及机制

The effects and mechanisms of Shexiangbaoxinwan on myocardial fibrosis in rats with pressure overload

目的:观察麝香保心丸(HMP)对压力超负荷大鼠心肌纤维化的防治作用并初步探讨其机制。方法:通过腹主动脉缩窄术制备压力超负荷大鼠心肌纤维化模型,随机选取60只成年雄性SD大鼠将其分成6组:假手术组、模型组、麝香保心丸22.5 mg/kg组、麝香保心丸45 mg/kg组、麝香保心丸90 mg/kg组、替米沙坦10mg/kg组。喂养8周后观察麝香保心丸对高血压大鼠心功能参数的影响;ELISA法测定血清TGF-β1的含量;Masson染色法观察心肌组织胶原纤维沉积情况,计算心肌胶原容积分数(CVF);免疫组织化学染色法测定TGF-β1蛋白表达情况,RT-PCR测定Smad3、Smad7mRNA表达情况。结果:麝香保心丸45 mg/kg剂量组能够改善压力超负荷大鼠心功能,降低血清TGF-β1的浓度,改善心肌组织胶原纤维沉积情况,减少大鼠心肌组织TGF-β1、Smad3mRNA的表达,上调Smad7mRNA的表达水平;麝香保心丸90 mg/kg剂量组较麝香保心丸45 mg/kg剂量组上述指标改善更佳明显,但麝香保心丸22.5 mg/kg剂量组无明显抑制心肌纤维化作用。结论:麝香保心丸可能在一定程度上通过抑制TGFβ-1/Smads信号转导通路的过度激活来抑制高血压心肌纤维化的发生。

Objective：To observe the effect of Shexiangbaoxinwan （SBW） on myocardial fibrosis in rats with pressure overload and discuss its mech- anism. Methods： To prepare the model of hypertensive myocardial fibrosis rat by abdominal aortic constriction. Randomly selected 60 adult male SD rats were divided into 6 groups, sham operation group, model group, Shexiangbaoxinwan （22.5mg/kg,45mg/kg and 90mg/kg dose three subgroups）, telmisartan 10mg/kg group （ as positive control）. After 8 weeks of feeding, observing the effect on the cardiac function pa- rameters of rats. ELISA method was used to determine the content of TGF-β1 in serum, and Masson staining method was used to observe the deposition of collagen fibers in myocardium and estimate collagen volume fraction, Immunohistochemistry staining method was used to deter- mine the expression of TGF-β1 protein. The expression level of Smad3 and Smad7 was determined by RT-PCR. Results：Shexiangbaoxinwan dJmg/kg dose groups have improved pressure overload rat cardiac function, reduced serum TGF-β1 concentrations, improved the myocardial collagen fibers deposition, reduced the expression level of TGF-β1 ,Smad3mRNA in myocardial tissue and increased the expression level of Smad7 mRNA, compared with the Shexiangbaoxinwan 45mg/kg dose group,the above indexs were improved significantly better in the Shex- iangbaoxinwan 90mg/kg dose group, But there was no significant improvement in the above indexes in Shexiangbaoxinwan 22.5mg/kg dose group. Conclusion： Shexiangbaoxinwan perhaps through inhibit the TGF-β1/Smads signal transduction pathway over activated to inhibit the occurrence of hypertensive myocardial fibrosis.