目的 基于蛋白激酶B（protein kinase B，Akt）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）及细胞外调节蛋白激酶（extracellular regulated protein kinases，ERK）/mTOR信号通路探究活心丸对心肌肥大大鼠自噬的影响。方法 SD大鼠ip盐酸异丙肾上腺素诱导心肌肥大，分别给予活心丸和盐酸普萘洛尔进行干预，检测大鼠超声心动图，采用ELISA法检测大鼠血清中心肌肥大指标心房钠尿肽（atrial natriuretic peptide，ANP）、脑钠肽（brain natriuretic peptide，BNP）及炎症因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）水平；采用苏木素-伊红（HE）和Masson染色观察大鼠心肌组织病理变化；采用免疫组化法检测大鼠心肌组织微管相关蛋白1轻链3（microtubule associated protein 1 light chain 3，LC3）蛋白表达情况；采用Western blotting法检测大鼠心肌组织ERK、磷酸化ERK（phosphorylated ERK，p-ERK）、Akt、p-Akt、mTOR、p-mTOR和LC3蛋白表达情况。结果 与模型组相比，各给药组大鼠心肌肥大缓解，心肌组织病理损伤减轻，血清中ANP、BNP、TNF-α和IL-6水平显著降低（P＜0.01、0.001）；心肌组织中p-ERK/ERK、p-Akt/Akt和p-mTOR/mTOR蛋白表达水平显著升高（P＜0.05、0.01），LC3 Ⅱ/LC3 I蛋白表达水平显著降低（P＜0.001）。结论 活心丸通过抑制自噬减轻大鼠心肌肥大，其机制可能与激活Akt/mTOR及ERK/mTOR通路相关。

Objective To explore the effect of Huoxin Pills (活心丸) on autophagy in rats with cardiac hypertrophy based on protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and extracellular regulated protein kinases (ERK)/mTOR signaling pathways. Methods SD rats were ip isoproterenol to induce cardiac hypertrophy, Huoxin Pills and propranolol hydrochloride were given for intervention, echocardiography of rats was detected, ELISA method was used to detect levels of cardiac hypertrophy indicators atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and inflammatory factors TNF-α and IL-6 in serum of rats; HE and Masson staining were used to observe the pathological changes of myocardial tissue in rats; Immunohistochemistry was used to detect microtubule associated protein 1 light chain 3 (LC3) protein expression in myocardial tissue of rats; Western blotting was used to detect the protein expressions of ERK, phosphorylated ERK (p-ERK), Akt, p-Akt, mTOR, p-mTOR and LC3 in myocardial tissue of rats. Results Compared with model group, myocardial hypertrophy of rats in each administration group was relieved, pathological damage of myocardial tissue was alleviated, and levels of ANP, BNP, TNF-α and IL-6 in serum were significantly decreased (P < 0.01, 0.001); Protein expression levels of p-ERK/ERK, p-Akt/Akt and p-mTOR/mTOR were significantly increased (P < 0.05, 0.01), and LC3 II/LC3 I protein expression level was significantly decreased (P < 0.001). Conclusion Huoxin Pills can reduce cardiac hypertrophy in rats by inhibiting autophagy, and its mechanism may be related to the activation of Akt/mTOR and ERK/mTOR pathways.

R285.5

广州市科技计划项目（202103000049）