目的 探究辣椒素对急性心肌梗死大鼠的保护作用及相关机制。方法 联合TCMSP、DAVID网站进行网络药理学分析，探寻辣椒素抗急性心肌梗死可能的作用靶点及通路。48只SD大鼠随机分为假手术组、模型组、辣椒素（20 mg/kg）组、辣椒素＋2-MeoE2（30 mg/kg）组，各组ig相应药物连续14 d，1次/d。采用心脏超声观察大鼠心肌功能的变化，试剂盒检测血清中心肌酶肌酸激酶（CK）、肌酸激酶同工酶MB（CK-MB）、乳酸脱氢酶（LDH）和心肌肌钙蛋白（cTnT）水平。苏木精–伊红（HE）染色观察心脏组织的组织学变化。实时荧光定量检测低氧诱导因子-1A（HIF-1A）、血管内皮生长因子（VEGF）、血红素加氧酶1（HMOX1）、B淋巴细胞瘤-2（Bcl-2）mRNA的表达。Western blotting检测大鼠心肌组织中HIF-1A、Bcl-2蛋白水平。结果 网络药理学研究分析显示辣椒素抗急性心肌梗死靶点富集显著性最高的通路为HIF-1信号通路。动物实验显示，与模型组相比，辣椒素组心肌细胞凋亡率明显减少，血清CK、CK-MB、LDH和cTnT水平均明显下降，左室舒张末期容积（LVEDV）、左室收缩末期容积（LVESV）明显下降，左室短轴的缩短率（LVFS）、左心室射血分数（LVEF）、每搏量（SV）明显增加（P＜0.05、0.01），同时HIF-1A、VEGF、HMOX1、Bcl-2 mRNA表达明显增加，HIF-1A、Bcl-2蛋白表达也明显升高（P＜0.01）。与辣椒素组相比，辣椒素＋2-MeoE2组对急性心肌梗死大鼠的保护作用明显减弱。结论 辣椒素可能通过调节HIF-1A、VEGF、HMOX1、Bcl-2等核心靶标，干预HIF-1等信号通路的活性，进而发挥抗急性心肌梗死的作用。

Objective To investigate the protective effect of capsaicin on acute myocardial infarction rats and its related mechanism. Methods Network pharmacologyanalysis was conducted in conjunction with TCMSP, DAVID and other websites to explore the possible action targets and pathways of capsaicin. Forty-eight SD rats were randomly divided into sham operation group, model group, capsaicin (20 mg/kg) group, and capsaicin + 2-MeoE2 (30 mg/kg) group. Each group was given the corresponding drug intragastrically for 14 days, once daily. The changes of myocardial function in rats with acute myocardial infarction were observed by echocardiography. Serum levels of CK, CK-MB, LDH, and cTnT were detected by the kit. HE staining was used to observe the histological changes of the heart tissue. Real-time fluorescence quantitative detection of HIF-1A, VEGF, HMOX1, Bcl-2 mRNA expression. The protein levels of HIF-1A and Bcl-2 in rat myocardia were detected by Western blotting. Results Network pharmacology analysis showed that the HIF-1 signaling pathway was the most significant pathway for capsaicin to inhibit the accumulation of targets in acute myocardial infarction. Animal experiments showed that compared with model group, the apoptosis rate of cardiomyocytes in capsaicin group was significantly reduced, serum CK, CK-MB, LDH and cTnT levels were significantly decreased, and left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were significantly decreased. The left ventricular short axis shortening rate (LVFS), left ventricular ejection fraction (LVEF) and stroke volume (SV) were significantly increased (P < 0.05, 0.01), while the mRNA expressions of HIF-1A, VEGF, HMOX1 and Bcl-2 were significantly increased. The expressions of HIF-1A and Bcl-2 were also significantly increased (P < 0.01). Compared with capsaicin group, the protective effect of capsaicin + 2-MeoE2 group on acute myocardial infarction rats was significantly weakened. Conclusion Capsaicin may interfere with the activity of HIF-1 and other signaling pathways by regulating HIF-1A, VEGF, HMOX1, Bcl-2 and other core targets, and thus play an anti-acute myocardial infarction role.

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