目的 探讨维拉帕米调节腺苷酸活化蛋白激酶（AMPK）/糖原合酶激酶-3β（GSK-3β）/核因子E2相关因子2（Nrf2）通路对急性心肌梗死大鼠的心肌保护作用。方法 将大鼠分为假手术组、模型组、维拉帕米（0.165、0.660 mg/kg）组、阿司匹林组及维拉帕米＋Compound C组，每组18只。建模成功1 h后立即给药处理，1次/d，共持续7 d。检测大鼠左室短轴缩短率（LVFS）和左室射血分数（LVEF）的变化；2,3,5-三苯基氯化四氮唑（TTC）染色检测心肌梗死率；HE染色检测心肌组织病理；试剂盒检测心肌组织中丙二醛（MDA）、肌钙蛋白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染色检测心肌细胞凋亡；Western blotting检测p-AMPK、p-GSK-3β、Nrf2蛋白。结果 与模型组相比，维拉帕米组心肌细胞紊乱程度有所改善，LVFS、LVEF、心肌组织中SOD活性及p-AMPK、p-GSK-3β、Nrf2蛋白表达显著升高，心肌梗死率、心肌组织中MDA、cTnI水平、CK-MB活性及心肌细胞凋亡率显著降低（P＜0.05），Compound C减弱了维拉帕米对急性心肌梗死大鼠心肌损伤的保护作用。结论 维拉帕米改善急性心肌梗死大鼠心肌损伤的机制可能与激活AMPK/GSK-3β/Nrf2通路有关。

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

四川省卫生健康委员医学科技项目(21PJ130)