目的 探討冠心舒通膠囊（GXST）通過(guò)調(diào)控心肌細(xì)胞凋亡改善心肌梗死的分子機(jī)制。方法 40只小鼠隨機(jī)分為5組，每組8只，分別為對(duì)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(duì)照組和模型組給予等體積0.5% CMC-Na溶液。除對(duì)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(dǎo)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(cè)量左心室相對(duì)壁厚（LV-RWT）和室間隔厚度（IVST）； TUNEL染色觀察心肌細(xì)胞凋亡；全自動(dòng)生化分析儀及相關(guān)配套試劑檢測(cè)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(shí)時(shí)熒光定量PCR（qRT-PCR）檢測(cè)心肌組織B淋巴細(xì)胞瘤-2（Bcl-2）、Bcl-2關(guān)聯(lián)X蛋白（Bax）、Caspase-3 mRNA相對(duì)表達(dá)量； Western blotting檢測(cè)Bcl-2、Bax、Caspase-3、cleaved Caspase-3、芳香烴受體（AHR）、肉瘤細(xì)胞來(lái)源的蛋白激酶（SRC）、p-SRC、細(xì)胞外調(diào)節(jié)蛋白激酶（ERK）、p-ERK蛋白表達(dá)。結(jié)果 與模型組比較，GXST組心肌組織病理?yè)p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(yáng)性細(xì)胞比例明顯減少（P＜ 0.05）； Caspase-3、Bax mRNA表達(dá)顯著降低（P＜0.05、0.01），Bcl-2 mRNA表達(dá)顯著增加（P＜0.05）； Bcl-2、AHR、p-SRC、p-ERK蛋白表達(dá)顯著增加（P＜0.05、0.01），Bax、cleaved-Caspase-3蛋白表達(dá)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(xì)胞凋亡，其機(jī)制與激活A(yù)HR/SRC/ERK信號(hào)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(guó)家自然科學(xué)基金項(xiàng)目（82204720）； 南京藥學(xué)會(huì)會(huì)企合作藥物臨床綜合評(píng)價(jià)科研專項(xiàng)資助項(xiàng)目（2023ZP10， 2023ZP05）