目的 探究辣椒素對急性心肌梗死大鼠的保護(hù)作用及相關(guān)機(jī)制。方法 聯(lián)合TCMSP、DAVID網(wǎng)站進(jìn)行網(wǎng)絡(luò)藥理學(xué)分析，探尋辣椒素抗急性心肌梗死可能的作用靶點(diǎn)及通路。48只SD大鼠隨機(jī)分為假手術(shù)組、模型組、辣椒素（20 mg/kg）組、辣椒素＋2-MeoE2（30 mg/kg）組，各組ig相應(yīng)藥物連續(xù)14 d，1次/d。采用心臟超聲觀察大鼠心肌功能的變化，試劑盒檢測血清中心肌酶肌酸激酶（CK）、肌酸激酶同工酶MB（CK-MB）、乳酸脫氫酶（LDH）和心肌肌鈣蛋白（cTnT）水平。蘇木精–伊紅（HE）染色觀察心臟組織的組織學(xué)變化。實(shí)時(shí)熒光定量檢測低氧誘導(dǎo)因子-1A（HIF-1A）、血管內(nèi)皮生長因子（VEGF）、血紅素加氧酶1（HMOX1）、B淋巴細(xì)胞瘤-2（Bcl-2）mRNA的表達(dá)。Western blotting檢測大鼠心肌組織中HIF-1A、Bcl-2蛋白水平。結(jié)果 網(wǎng)絡(luò)藥理學(xué)研究分析顯示辣椒素抗急性心肌梗死靶點(diǎn)富集顯著性最高的通路為HIF-1信號通路。動(dòng)物實(shí)驗(yàn)顯示，與模型組相比，辣椒素組心肌細(xì)胞凋亡率明顯減少，血清CK、CK-MB、LDH和cTnT水平均明顯下降，左室舒張末期容積（LVEDV）、左室收縮末期容積（LVESV）明顯下降，左室短軸的縮短率（LVFS）、左心室射血分?jǐn)?shù)（LVEF）、每搏量（SV）明顯增加（P＜0.05、0.01），同時(shí)HIF-1A、VEGF、HMOX1、Bcl-2 mRNA表達(dá)明顯增加，HIF-1A、Bcl-2蛋白表達(dá)也明顯升高（P＜0.01）。與辣椒素組相比，辣椒素＋2-MeoE2組對急性心肌梗死大鼠的保護(hù)作用明顯減弱。結(jié)論 辣椒素可能通過調(diào)節(jié)HIF-1A、VEGF、HMOX1、Bcl-2等核心靶標(biāo)，干預(yù)HIF-1等信號通路的活性，進(jìn)而發(fā)揮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.

R285