目的 探討維拉帕米調(diào)節(jié)腺苷酸活化蛋白激酶（AMPK）/糖原合酶激酶-3β（GSK-3β）/核因子E2相關(guān)因子2（Nrf2）通路對急性心肌梗死大鼠的心肌保護(hù)作用。方法 將大鼠分為假手術(shù)組、模型組、維拉帕米（0.165、0.660 mg/kg）組、阿司匹林組及維拉帕米＋Compound C組，每組18只。建模成功1 h后立即給藥處理，1次/d，共持續(xù)7 d。檢測大鼠左室短軸縮短率（LVFS）和左室射血分?jǐn)?shù)（LVEF）的變化；2,3,5-三苯基氯化四氮唑（TTC）染色檢測心肌梗死率；HE染色檢測心肌組織病理；試劑盒檢測心肌組織中丙二醛（MDA）、肌鈣蛋白I（cTnI）水平及肌酸激酶同工酶（CK-MB）、超氧化物歧化酶（SOD）活性；TUNEL染色檢測心肌細(xì)胞凋亡；Western blotting檢測p-AMPK、p-GSK-3β、Nrf2蛋白。結(jié)果 與模型組相比，維拉帕米組心肌細(xì)胞紊亂程度有所改善，LVFS、LVEF、心肌組織中SOD活性及p-AMPK、p-GSK-3β、Nrf2蛋白表達(dá)顯著升高，心肌梗死率、心肌組織中MDA、cTnI水平、CK-MB活性及心肌細(xì)胞凋亡率顯著降低（P＜0.05），Compound C減弱了維拉帕米對急性心肌梗死大鼠心肌損傷的保護(hù)作用。結(jié)論 維拉帕米改善急性心肌梗死大鼠心肌損傷的機(jī)制可能與激活A(yù)MPK/GSK-3β/Nrf2通路有關(guān)。

Objective To investigate the myocardial protective effect of verapamil on acute myocardial infarction rats by regulating the AMPK/GSK-3β/Nrf2 pathway. Methods The rats were divided into sham operation group, model group, verapamil (0.165 and 0.660 mg/kg) group, verapamil + Compound C group, with 18 rats in each group. After successful modeling for 1 h, they were immediately administered once daily for 7 days. The changes in LVFS and LVEF in rats were detected, 2,3,5-triphenyltetrazolium chloride staining was applied to detect the percentage of myocardial infarction area, HE staining was applied to detect pathological changes in myocardial tissue, the levels of MDA and cTnI and the activities of CK-MB and SOD in myocardial tissue were detected by the kit. TUNEL staining detect myocardial cell apoptosis, Western blotting detect p-AMPK, p-GSK-3β, and Nrf2 proteins in myocardial tissue. Results Compared with model group, the degree of myocardial cell disruption in the verapamil group was improved, the LVFS, LVEF, activities of SOD and the expression of p-AMPK, p-GSK-3β, and Nrf2 proteins in myocardial tissue increased, the percentage of myocardial infarction area, levels of MDA, cTnI , activities of CK-MB in myocardial tissue, and apoptosis rate of myocardial cells decreased (P < 0.05). Compound C weakened the protective effect of verapamil on myocardial injury in acute myocardial infarction rats. Conclusion The mechanism of verapamil improving myocardial injury in acute myocardial infarction rats may be related to the activation of the AMPK/GSK-3β/Nrf2 pathway.

R972

四川省衛(wèi)生健康委員醫(yī)學(xué)科技項(xiàng)目(21PJ130)