目的 探讨冠心舒通胶囊（GXST）通过调控心肌细胞凋亡改善心肌梗死的分子机制。方法 40只小鼠随机分为5组，每组8只，分别为对照组、模型组和GXST低、中、高剂量（0.5、1.0、2.0 g·kg^-1）组，连续6 d ig给药，对照组和模型组给予等体积0.5% CMC-Na溶液。除对照组外，其他组在第5、6天给小鼠sc异丙肾上腺素（ISO，150 mg·kg^-1）诱导心肌梗死模型。在最后1次sc ISO后16 h，将小鼠麻醉并处死。苏木精-伊红（HE）染色观察小鼠心肌组织病理变化，使用NIS-Elements BR版采图软件测量左心室相对壁厚（LV-RWT）和室间隔厚度（IVST）； TUNEL染色观察心肌细胞凋亡；全自动生化分析仪及相关配套试剂检测血清心肌肌钙蛋白T（cTnT）、乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）、肌酸激酶（CK）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平；实时荧光定量PCR（qRT-PCR）检测心肌组织B淋巴细胞瘤-2（Bcl-2）、Bcl-2关联X蛋白（Bax）、Caspase-3 mRNA相对表达量； Western blotting检测Bcl-2、Bax、Caspase-3、cleaved Caspase-3、芳香烃受体（AHR）、肉瘤细胞来源的蛋白激酶（SRC）、p-SRC、细胞外调节蛋白激酶（ERK）、p-ERK蛋白表达。结果 与模型组比较，GXST组心肌组织病理损伤明显减轻，LV-RWT和IVST显著降低（P＜0.05、0.01）；血清中CK、CK-MB、AST、cTnT、LDH、ALT水平显著下降（P＜ 0.01）； TUNEL阳性细胞比例明显减少（P＜ 0.05）； Caspase-3、Bax mRNA表达显著降低（P＜0.05、0.01），Bcl-2 mRNA表达显著增加（P＜0.05）； Bcl-2、AHR、p-SRC、p-ERK蛋白表达显著增加（P＜0.05、0.01），Bax、cleaved-Caspase-3蛋白表达显著降低（P＜0.05、0.01）。结论 GXST能够缓解心肌梗死小鼠心肌损伤，抑制心肌细胞凋亡，其机制与激活AHR/SRC/ERK信号通路相关。

Objective To investigate the molecular mechanism of Guanxin Shutong Capsule (GXST) in the treatment of myocardial infarction by regulating myocardial cell apoptosis. Methods Forty mice were randomly divided into five groups, with eight mice in each group: the control group, the model group, and the low-, medium-, and high-dose GXST groups (0.5, 1.0, and 2.0 g·kg^-1). The mice were ig administered for six consecutive days. The control group and the model group were given the same volume of 0.5% CMC-Na solution. Except for the control group, the other groups were subcutaneously injected with isoproterenol (ISO, 150 mg·kg^-1) on the fifth and sixth days to induce myocardial infarction models. Sixteen hours after the last subcutaneous injection of ISO, the mice were anesthetized and sacrificed. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of myocardial tissue. The left ventricular relative wall thickness (LV-RWT) and interventricular septal thickness (IVST) were measured using NIS-Elements BR software. TUNEL staining was used to observe myocardial cell apoptosis. The levels of serum cardiac troponin T (cTnT), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected using an automatic biochemical analyzer and related reagents. The relative expression levels of Bcl-2, Bax, and Caspase-3 mRNA in myocardial tissue were detected by real-time fluorescence quantitative PCR (qRT-PCR). The protein expressions of Bcl-2, Bax, Caspase-3, cleaved-Caspase-3, aryl hydrocarbon receptor (AHR), src kinase (SRC), p-SRC, extracellular regulated protein kinase (ERK), and p-ERK were detected by Western blotting. Results Compared with the model group, the myocardial tissue pathological damage in the GXST groups was significantly alleviated, and LV-RWT and IVST were significantly reduced (P <0.05, 0.01); the levels of CK, CK-MB, AST, cTnT, LDH, and ALT in serum were significantly decreased (P <0.01); the proportion of TUNEL-positive cells was significantly reduced (P <0.05); the expressions of Caspase-3 and Bax mRNA were significantly decreased (P <0.05, 0.01), and the expression of Bcl-2 mRNA was significantly increased (P <0.05); the protein expressions of Bcl-2, AHR, p-SRC, and p-ERK were significantly increased (P <0.05, 0.01), and the protein expressions of Bax and cleaved Caspase-3 were significantly decreased (P <0.05, 0.01). Conclusion GXST can alleviate myocardial injury in mice with myocardial infarction and inhibit myocardial cell apoptosis, and its mechanism is related to the activation of the AHR/SRC/ERK signaling pathway.

R285.5

国家自然科学基金项目（82204720）； 南京药学会会企合作药物临床综合评价科研专项资助项目（2023ZP10， 2023ZP05）