二甲双胍对脓毒症大鼠心肌损伤的保护作用研究  

Protective effect of metformin against myocardial injury in septic rats

作　　者：艾波[1] 李文强[1] Ai Bo;Li Wen-qiang.(Department of Emergency,Remin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院急诊科,湖北武汉430060

出　　处：《中国急救医学》2018年第12期1105-1108,F0003,共5页Chinese Journal of Critical Care Medicine

摘　　要：目的采用大鼠盲肠结扎穿孔术(cecal ligation and puncture,CLP)建立脓毒症大鼠模型,观察二甲双胍对脓毒症大鼠心肌损伤的保护作用及其作用机制。方法取60只Wistar雄性大鼠,随机平均分成4组:Sham组、Sham/M组、CLP组、CLP/M组,每组设术后12、24h两个时间点。Sham组仅开腹取出盲肠翻动后还纳腹腔,不进行结扎和穿孔;Sham/M组在术前1.5h通过灌胃灌人二甲双胍(100mg/kg),其他同Sham组;CLP组采用CLP方法制备脓毒症模型;CLP/M组在术前1.5h通过灌胃灌入二甲双胍(100mg/kg),其他同CLP组。分别采血检测ALT、AST、cT水平;ELISA测定法检测心肌匀浆组织中TNF-α、IL-1β、cTnI的表达水平;TUNEL法染色检测术后24h心肌细胞凋亡的情况。结果①在术后12、24h,大鼠血浆ALT、AST、Cr、TNF-α、IL-1β、cTnI水平在Sham组与Sham/M组比较差异无统计学意义(P>0.05),在CLP组和CLP/M组明显升高(P<0.01),而且CLP/M组较CLP组明显降低(P<0.01);②Sham组(2.71%)和Sham/M组(2.81%)大鼠心肌细胞凋亡指数(AI)值比较差异无统计学意义(P>0.05);CLP组(21.28%)大鼠心肌细胞AI值较Sham组(2.71%)明显上升(P<0.01),CLP/M组(16.80%)较CLP组(21.28%)AI值明显下降(P<0.01)。结论二甲双胍对CLP模型大鼠心肌损伤具有明显的保护作用。Objective Rat sepsis model was made by cecal ligation and puncture (CLP) technique in order to observe the treatment of mefformin on myocardial injury in septic rats and to explore its potential mechanism.Methods 60 male Wistar rats were divided into four groups randomly:Sham group,Sham/M group,CLP,CLP/M group.Each group was divided into 12,24h observation subgroups.Sham group was only opened the abdomen to take out the appendix,then turned back into the abdominal cavity without ligation and perforation.Sham/M group animals were administered with metformin (100mg/kg)in lavage way 1.5h before operation,and the others were the same as the Sham group.The CLP group was sepsis model by CLP technique.CLP/M group animals were administered with naefformin (100mg/kg)in lavage way 1.5h before operation,and the others were the same as the CLP group.Blood level of ALT,AST,Cr was detected in each group at the observation time point respectively;ELISA was used to detect serum TNF -α,IL-1β,cTnI expression level;TUNEL method was used to detect myocardial cell apoptosis.Results ①At 12,24h,the Sham group and Sham/M group rats did not show obvious differences in serum ALT,AST,Cr,TNF -α,IL -1β,cTnI levels (P >0.05);compared with the control group,the serum ALT,AST,Cr levels in CLP group and CLP/M group rats increased significantly (P <0.01);at the same time,the CLP/M group level decreased significantly compared with the CLP group (P <0.01).②The Sham group (2.71%)and Sham/M group (2.81%)did not show obvious difference in myocardial cells AI value (P >0.05);The myocardial cells AI value increased obviously in CLP group(21.28%)compared with the Sham group(P <0.01); and AI value in CLP/M group (16.8%)decreased significantly compared with,the"CLP group (P < 0.01).Conclusion Metformin has significant protective effect against myocardial injury in CLP model rats.

关 键 词：二甲双胍 脓毒症 盲肠结扎穿孔术(CLP) 心肌损伤 

分 类 号：R285.5[医药卫生—中药学]