褪黑素介导腺苷酸活化蛋白激酶抑制线粒体损伤降低大鼠心肌缺血再灌注损伤的机制  

Mechanism of melatonin mediated adenylate activated protein kinase inhibition of mitochondrial injury and reduction of myocardial ischemia-reperfusion injury in rats

作　　者：曾明辉 余龙辉 邱明涛 李晨 ZENG Minghui;YU Longhui;QIU Mingtao;LI Chen(The Second Department of Cardiovascular Medicine,Pingxiang People's Hospital,Jiangxi Province,Pingxiang337000,China;Department of Cardiovascular Medicine,Jiangxi Provincial People's Hospital,Jiangxi Province,Nanchang330000,China)

机构地区：[1]江西省萍乡市人民医院心血管内科二科,江西萍乡337000 [2]江西省人民医院心血管内科,江西南昌330000

出　　处：《中国当代医药》2025年第6期10-15,共6页China Modern Medicine

基　　金：江西省卫生健康委科技计划项目(202410765)。

摘　　要：目的探究褪黑素(Mel)介导腺苷酸活化蛋白激酶(AMPK)通路对心肌缺血/再灌注损伤(MI/RI)的保护机制。方法选取50只无特定病原体(SPF)级雄性SD大鼠作为研究对象,随机分为5组,每组10只,其中假手术组(Sham组)不结扎冠状动脉左前降支;Mel组不结扎冠状动脉左前降支,腹腔单次注射褪黑素;溶剂(V)对照组(MI/RI+V组)采用冠状动脉结扎法造模,造模前及再灌注前腹腔注射乙醇-生理盐水;Mel治疗组(MI/RI+Mel组)造模前及再灌注前腹腔注射褪黑素;Mel+AMPK抑制剂BML275处理组(MI/RI+Mel+BML275组)造模前及再灌注前腹腔注射BML275,再灌注前腹腔注射褪黑素。采用冠状动脉结扎法建立MI/RI模型,苏木素-伊红(HE)染色法观察病理结果,检测大鼠心功能和血清肌钙蛋白T(TnT)、乳酸脱氢酶(LDH)、肌酸激酶(CK)水平。Evans blue-2,3,5-氯化三苯基四氮唑(TTC)双染法观察心肌梗死情况。Western blot检测心肌组织腺苷酸活化蛋白激酶α(AMPKα)、线粒体动力相关蛋白(Drp1)和细胞色素C(Cyt C)表达。结果MI/RI+Mel组、MI/RI+Mel+BML275组的左心室射血分数(LVEF)和左心室缩短分数(LVFS)均高于MI/RI+V组,MI/RI+Mel+BML275组的LVEF和LVFS均低于MI/RI+Mel组,差异有统计学意义(P<0.05)。MI/RI+Mel组、MI/RI+Mel+BML275组的血清TnT、CK、LDH水平均低于MI/RI+V组,MI/RI+Mel+BML275组的血清TnT、CK、LDH水平均高于MI/RI+Mel组,差异有统计学意义(P<0.05)。MI/RI+Mel组、MI/RI+Mel+BML275组的心肌梗死面积均小于MI/RI+V组,MI/RI+Mel+BML275组的心肌梗死面积大于MI/RI+Mel组,差异有统计学意义(P<0.05)。MI/RI+Mel组、MI/RI+Mel+BML275组的磷酸化腺苷酸活化蛋白激酶α(p-AMPKα)表达均高于MI/RI+V组,MI/RI+Mel+BML275组的p-AMPKα表达低于MI/RI+Mel组,差异有统计学意义(P<0.05)。MI/RI+Mel组、MI/RI+Mel+BML275组的磷酸化线粒体动力相关蛋白(p-Drp1)/Drp1和Cyt C表达均低于MI/RI+V组,MI/RI+Mel+BML275组的p-Drp1/Drp1和Cyt C表达均高于MI/RI+Mel�Objective To explore the protective mechanism of melatonin(Mel)mediated adenosine 5'-monophosphate-activated protein kinase(AMPK)pathway against myocardial ischemia/reperfusion injury(MI/RI).Methods A total of 50 SPF grade male SD rats were selected as research subjects,and they were randomly divided into 5 groups,with 10 rats in each group.In Sham operation group,the left anterior descending coronary artery was not ligated.In the Mel group,the left anterior descending coronary artery was not ligated,and a single intraperitoneal injection of melatonin was given.The vehicle(V)control group(MI/RI+V group)was established by coronary artery ligation,and ethanol-saline was injected intraperitoneally before modeling and reperfusion.In the Mel treatment group(MI/RI+Mel group),melatonin was injected intraperitoneally before modeling and reperfusion.In MI/RI+Mel+BML275 group,BML275 was intraperitoneally injected before modeling and reperfusion,and melatonin was intraperitoneally injected before reperfusion.A MI/RI model was established by coronary artery ligation,and the pathological results were observed by hematoxylin-eosin(HE)staining.The cardiac function and serum levels of troponin T(TnT),lactate dehydrogenase(LDH),and creatine kinase(CK)were detected in rats.Evans blue-triphenyltetrazolium chloride(TTC)double staining method was used to observe myocardial infarction.Western blot was used to detect the expression of adenosine 5'-monophosphate-activated protein kinase(AMPKα),dynamin-related protein 1(Drp1),and cytochrome C(Cyt C)in myocardial tissue.Results The left ventricular ejection fraction(LVEF)and left ventricular shortening fraction(LVFS)of the MI/RI+Mel group and the MI/RI+Mel+BML275 group were higher than those of the MI/RI+V group,while the LVEF and LVFS of the MI/RI+Mel+BML275 group were lower than those of the MI/RI+Mel group,with statistically significant differences(P<0.05).The serum TnT,CK,and LDH levels in the MI/RI+Mel group and MI/RI+Mel+BML275 group were lower than those in the MI/RI+V group,while

关 键 词：褪黑素 心肌缺血/再灌注损伤 大鼠 腺苷酸活化蛋白激酶通路 线粒体损伤 

分 类 号：R542.2[医药卫生—心血管疾病]