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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 preventive and therapeutic effects of Shexiang Baoxin Pill (HMP) on myocardial fibrosis in rats with pressure overload and to explore its mechanism. Methods: A rat model of myocardial fibrosis was established by abdominal aortic constriction. Sixty adult male Sprague-Dawley rats were randomly divided into 6 groups: sham operation group, model group, Shexiang Baoxin Pill (22.5 mg / kg) Group, 45 mg / kg group of Shexiang Baoxin Pill, 90 mg / kg group of Shexiang Baoxin Pill, 10 mg / kg group of telmisartan. After 8 weeks of feeding, the effect of Shexiang Baoxin Pill on the cardiac function parameters in hypertensive rats was observed. The content of TGF-β1 in serum was measured by ELISA. The deposition of collagen fibers in myocardium was observed by Masson staining and the myocardial collagen volume fraction (CVF) was calculated. The expression of TGF-β1 protein was detected by immunohistochemical staining. The expression of Smad3 and Smad7 mRNA was detected by RT-PCR. Results: Shexiang Baoxin Pill 45 mg / kg dose group could improve cardiac function, decrease serum TGF-β1 concentration, improve collagen deposition in myocardium and decrease expression of TGF-β1 and Smad3 in rat myocardium , Up-regulated the expression of Smad7mRNA; Shexiang Baoxin Pill 90 mg / kg dose group than the Shexiang Baoxin Pill 45 mg / kg dose group improved more significantly above indicators, but the Shexiang Baoxin Pill 22.5 mg / kg dose group had no significant inhibition of heart Muscle fibrosis. Conclusion: Shexiang Baoxin Pill may inhibit the occurrence of hypertensive myocardial fibrosis by inhibiting the over-activation of TGFβ-1 / Smads signal transduction pathway to a certain extent.