目的 探討冠心舒通膠囊（GXST）通過調(diào)控心肌細胞凋亡改善心肌梗死的分子機制。方法 40只小鼠隨機分為5組，每組8只，分別為對照組、模型組和GXST低、中、高劑量（0.5、1.0、2.0 g·kg^-1）組，連續(xù)6 d ig給藥，對照組和模型組給予等體積0.5% CMC-Na溶液。除對照組外，其他組在第5、6天給小鼠sc異丙腎上腺素（ISO，150 mg·kg^-1）誘導心肌梗死模型。在最后1次sc ISO后16 h，將小鼠麻醉并處死。蘇木精-伊紅（HE）染色觀察小鼠心肌組織病理變化，使用NIS-Elements BR版采圖軟件測量左心室相對壁厚（LV-RWT）和室間隔厚度（IVST）； TUNEL染色觀察心肌細胞凋亡；全自動生化分析儀及相關(guān)配套試劑檢測血清心肌肌鈣蛋白T（cTnT）、乳酸脫氫酶（LDH）、肌酸激酶同工酶（CK-MB）、肌酸激酶（CK）、丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）水平；實時熒光定量PCR（qRT-PCR）檢測心肌組織B淋巴細胞瘤-2（Bcl-2）、Bcl-2關(guān)聯(lián)X蛋白（Bax）、Caspase-3 mRNA相對表達量； Western blotting檢測Bcl-2、Bax、Caspase-3、cleaved Caspase-3、芳香烴受體（AHR）、肉瘤細胞來源的蛋白激酶（SRC）、p-SRC、細胞外調(diào)節(jié)蛋白激酶（ERK）、p-ERK蛋白表達。結(jié)果 與模型組比較，GXST組心肌組織病理損傷明顯減輕，LV-RWT和IVST顯著降低（P＜0.05、0.01）；血清中CK、CK-MB、AST、cTnT、LDH、ALT水平顯著下降（P＜ 0.01）； TUNEL陽性細胞比例明顯減少（P＜ 0.05）； Caspase-3、Bax mRNA表達顯著降低（P＜0.05、0.01），Bcl-2 mRNA表達顯著增加（P＜0.05）； Bcl-2、AHR、p-SRC、p-ERK蛋白表達顯著增加（P＜0.05、0.01），Bax、cleaved-Caspase-3蛋白表達顯著降低（P＜0.05、0.01）。結(jié)論 GXST能夠緩解心肌梗死小鼠心肌損傷，抑制心肌細胞凋亡，其機制與激活AHR/SRC/ERK信號通路相關(guān)。

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

國家自然科學基金項目（82204720）； 南京藥學會會企合作藥物臨床綜合評價科研專項資助項目（2023ZP10， 2023ZP05）