加参方通过抑制TGF-β/Smads信号转导通路改善大鼠心肌梗死后心室重构的机制

Mechanism of Jiashen Formula on improving rat model of ventricular remodeling after myocardial infarction via inhibiting TGF-β/Smads pathway

目的:观察加参方对大鼠心肌梗死早期心室重构及TGF-β/Smads信号转导通路的影响作用,探讨其抑制心室重构的相关机制。方法:建立大鼠急性心肌梗死模型后,随机分为模型组、加参方3g组、加参方6g组和氯沙坦组,另设假手术组。药物干预组在心肌梗死发生24h后灌胃给药。4周后利用心脏B超、病理组织学染色和Western blot技术分别确定加参方对大鼠心功能、心脏胶原蛋白含量和TGF-β/Smads信号转导通路的影响作用。结果:与模型组比较,加参方6g组能够明显抑制左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD)的扩大和舒张期左室后壁厚度(PWT)的变薄,提高左室射血分数(LVEF)和左室短轴缩短率(LVFS)(P<0.05);加参方能降低缺血危险区胶原蛋白的含量(P<0.05),该作用呈剂量依赖性;降低心肌组织中转化生长因子-β1(TGF-β1)、磷酸化的Smad2和磷酸化的Smad3的蛋白表达(P<0.05),该作用呈剂量依赖性。结论:加参方能改善心功能,抑制心肌纤维化,从而起到改善心肌梗死早期心室重构的作用,其相关机制可能与抑制TGF-β/Smads信号转导通路有关。

Objective: To investigate the effects of Jiashen Formula(JSF) on inhibiting rat model of ventricular remodeling after myocardial infarction(MI) via inhibiting TGF-β/Smads pathway. Methods: The acute MI model rats were randomly divided into the model group, JSF at the dose of 3g group, JSF at the dose of 6g group and losartan group. The drug intervention groups were treated by gavage at 24 h after MI, for 4 weeks. The cardiac function was determined by heart B ultrasonography. The effects of JSF on collagen protein and TGF-β/Smads signaling pathway were detected by histopathological staining and Western blot, respectively. Results: Compared with the model group, treatment with JSF at the dose of 6g·kg^(-1)·day-1reduced left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter(LVESD), and enhanced left ventricular ejection fraction(LVEF) and left ventricular fractional shorten(LVFS)(P<0.05). The level of collagen protein was decreased by treatment with JSF(P<0.05) and the effects showed a dose-dependent manner. The expression of transforming growth factor-β1(TGF-β1), phosphorylated Smad 2(p-Smad 2), and phosphorylated Smad 3(p-Smad 3) were reduced by treatment with JSF(P<0.05) and the effects also showed a dose-dependent manner. Conclusion: JSF can improve the cardiac function and inhibit myocardial fibrosis, consequently improving the ventricular remodeling in early myocardial infarction, which partly was related to the inhibition of TGF-β/Smads signaling pathway.