摘要
目的观察二甲双胍通过腺苷酸活化蛋白激酶(AMPK)-Nod样受体家族包含pyrin结构域蛋白3(NLRP3)对大鼠心肌缺血再灌注损伤的影响。方法成年SD大鼠随机数字表法分为对照组、模型组和二甲双胍组,采用结扎左冠状动脉前降支构建大鼠心肌缺血再灌注损伤模型。二甲双胍组大鼠建模前灌胃给于二甲双胍250 mg/kg,对照组和模型组给与等体积生理盐水。3组大鼠再灌注2 h后,采用生化酶法检测心肌损伤标志物酸激酶(CK-MB)和肌钙蛋白Ⅰ(cTnⅠ);采用氯化三苯基四氮唑(TTC)染色和原位缺口末端标记法(TUNEL)染色分析大鼠心肌组织梗死面积和凋亡指数;采用酶联免疫吸附测定(ELISA)分析白细胞介素(IL)-1β和IL-18的表达水平;采用蛋白质印迹法(Western blot)分析大鼠心肌组织AMPK、NLRP3和半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-1表达水平。计量组数比较采用单因素方差分析。结果二甲双胍组大鼠心肌梗死比例[(26.14±4.71)%]明显低于模型组大鼠心肌梗死比例[(43.74±15.00)%],差异有统计学意义(t=3.540,P<0.05)。二甲双胍组大鼠血清CK-MB和cTnⅠ水平[(1821.88±213.52)U/L、(1.45±0.13)ng/L]明显低于对照组[(3100.87±149.41)U/L、(3.08±0.25)ng/L],差异有统计学意义(t=15.520、18.240,P<0.05)。二甲双胍组大鼠心肌凋亡比例[(10.56±2.36)%]明显低于模型组大鼠心肌凋亡比例[(27.43±3.90)%],差异有统计学意义(t=11.710,P<0.05)。二甲双胍组大鼠心肌组织磷酸化AMPK表达水平(1.22±0.11)明显高于对照组和模型组大鼠心肌组织(0.59±0.08、0.81±0.06),差异有统计学意义(t=14.370、10.510,P<0.05)。二甲双胍组大鼠心肌组织NLRP3和Caspase-1蛋白表达水平(1.19±0.15、1.24±0.10)明显低于模型组大鼠心肌组织(1.78±0.12、1.82±0.16),差异有统计学意义(t=9.895、9.554,P<0.05)。二甲双胍组大鼠血清IL-1β和IL-18水平[(98.20±7.25)、(94.90±8.57)pg/ml]明显低于模型组大鼠血清IL-1β和IL
Objective To investigate the effect of metformin on myocardial ischemia-reperfusion injury in rats through adenosine monophosphate-actived protein kinase(AMPK)-NLR family,pyrin domain containing 3(NLRP3).Methods Adult SD rats were randomly divided into control group,model group and metformin group by random number table..The myocardial ischemia-reperfusion injury model was established by ligating the anterior descending branch of left coronary artery.The rats in the metformin group were given 250 mg/kg metformin by gavage before modeling,and the control group and the model group were given the same volume of normal saline.Two hours after reperfusion,creatine kinase isoenzymes(CK-MB)and cardiac troponinⅠ(CTNⅠ)were detected by biochemical enzyme method.The infarct size and apoptosis index of rat myocardial tissue were analyzed by tovanto transit commission(TTC)staining and terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining.The expression level interleukin(IL)-1βand of IL-18 was analyzed by enzyme linked immunosorbent assay(ELISA).The expression levels of AMPK,NLRP3 and caspase-1 were analyzed by Western blotting.The number of measurement groups was compared by one-way ANOVA.Results The ratio of myocardial infarction in rats in metformin group[(26.14±4.71)%]was significantly lower than that in model group[(43.74±15.00)%,t=3.540,P<0.05].The serum CK-MB and CTNⅠlevels of rats in metformin group[(1821.88±213.52)U/L,(1.45±0.13)ng/L]were significantly lower than those in the control group[(3100.87±149.41)U/L,(3.08±0.25)ng/L,t=15.520,18.240,P<0.05].The ratio of myocardial apoptosis in rats in metformin group[(10.56±2.36)%]was significantly lower than that in model group[(27.43±3.90)%,t=11.710,P<0.05].The expression level of phosphorylated AMPK in the myocardium of rats in metformin group(1.22±0.11)was significantly higher than that in the control group and model group(0.59±0.08,0.81±0.06,t=14.370,10.510,P<0.05).The expression levels of NLRP3 and caspase-1 protein in the myoca
作者
杜娟娟
丁守坤
沈淑馨
谷广明
罗萍
Du Juanjuan;Ding Shoukun;Shen Shuxin;Gu Guangming;Luo Ping(Cardiovascular Comprehensive Ward,Henan Provincial People′s Hospital,Zhengzhou 450000,China)
出处
《中华实验外科杂志》
CAS
北大核心
2022年第10期1940-1943,共4页
Chinese Journal of Experimental Surgery
