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目的:研究苦参碱对异丙肾上腺素致大鼠心肌肥厚的保护作用及其对mTOR/p70S6K信号通路的调控。方法:大鼠皮下注射异丙肾上腺素建立慢性病理性心肌肥厚模型,将大鼠随机分为正常对照组、异丙肾上腺素(ISO)模型组、苦参碱(50,100,200 mg·kg-1·d-1)+ISO组和单用苦参碱(200 mg·kg-1·d-1)组。HE染色观察心肌病理变化;Western blot检测左心室组织中mTOR/p70S6K信号通路相关蛋白的表达。结果:与正常对照组比较,ISO模型组大鼠的心肌细胞肥大、排列紊乱,可见不同程度的纤维化、间质水肿和炎细胞浸润;苦参碱(50,100,200 mg·kg-1·d-1)可减轻大鼠心肌细胞肥大、纤维化、间质水肿和炎细胞浸润等ISO致心肌组织病理学结构的异常改变。与正常对照组相比,ISO模型组心肌组织内p-mTOR、p-p70S6K和p70S6K的表达显著增加;苦参碱(50,100,200 mg·kg-1)可逆转ISO致大鼠心肌组织中p70S6K表达的上调,同时下调mTOR Ser2448和p70S6K Thr389位点的磷酸化水平,且呈剂量依赖性;mTOR表达在各组之间均无差异;单用苦参碱组与正常对照组比较无显著性差异。结论:苦参碱具有抑制ISO致大鼠心肌肥厚的作用,其机制与抑制mTOR/p70S6K信号通路有关。
AIM: To investigate the protective effects of matrine on isoproterenol-induced cardiac hypertrophy and its regulation of mTOR / p70S6K signaling pathway. Methods: Chronic pathological myocardial hypertrophy model was established by subcutaneous injection of isoprenaline in rats. The rats were randomly divided into normal control group, isoproterenol (ISO) model group, matrine (50,100,200 mg · kg-1 · d- 1) + ISO group and matrine alone (200 mg · kg-1 · d-1) group. The pathological changes of myocardium were observed by HE staining. The expression of mTOR / p70S6K signal pathway related protein in left ventricular tissue was detected by Western blot. Results: Compared with the normal control group, the cardiomyocytes in the ISO model group were hypertrophy and disorganized, with varying degrees of fibrosis, interstitial edema and infiltration of inflammatory cells. Matrine (50, 100, 200 mg · kg -1 · d -1 ) Can relieve the abnormal changes of cardiac myocyte histopathology such as hypertrophy, fibrosis, interstitial edema and infiltration of inflammatory cells in rat cardiomyocytes. Compared with the normal control group, the expression of p-mTOR, p-p70S6K and p70S6K in myocardium of ISO model group increased significantly. Matrine (50,100,200 mg · kg-1) reversed the expression of p70S6K in ISO induced myocardial tissue Up-regulated, and down-regulated the phosphorylation levels of mTOR Ser2448 and p70S6K Thr389 sites in a dose-dependent manner. There was no difference in the expression of mTOR among all groups. There was no significant difference between the two groups in the matrine alone group and the normal control group. Conclusion: Matrine can inhibit cardiac hypertrophy induced by ISO in rats. Its mechanism is related to the inhibition of mTOR / p70S6K signaling pathway.