七氟醚后处理减轻大鼠心肌缺血再灌注损伤时Drp1与mito-KATP通道的关系  

Relationship between Drp1 and mito-KATP channel during sevoflurane postconditioning-induced reduction of myocardial ischemia-reperfusion injury in rats

作　　者：贺建东[1] 韩冲芳[1] 王一珍 雒珉[1] 王晓鹏[1] 杨文曲[1] 周晓辉 He Jiandong;Han Chongfang;Wang Yizhen;Luo Min;Wang Xiaopeng;Yang Wenqu;Zhou Xiaohui(Department of Anesthesiology,Shanxi Academy of Medical Sciences Shanxi Bethune Hospital,Taiyuan 030032,China;Department of Anesthesiology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医学科学院山西白求恩医院麻醉科,太原030032 [2]山西医科大学麻醉学院,太原030001

出　　处：《中华麻醉学杂志》2019年第12期1441-1444,共4页Chinese Journal of Anesthesiology

基　　金：山西省卫生和计划生育委员会科研课题(2015002)。

摘　　要：目的探讨七氟醚后处理减轻大鼠心肌缺血再灌注损伤时线粒体动力相关蛋白(Drp1)与线粒体ATP敏感性钾通道(mito-KATP通道)的关系。方法清洁级健康成年雄性SD大鼠40只,体重220~280 g,采用随机数字表法分为5组(n=8):假手术组(S组)、心肌缺血再灌注组(I/R组)、七氟醚后处理组(S-Post组)、七氟醚后处理+5-羟基癸酸组(S-Post+5-HD组)和七氟醚后处理+二甲基亚砜组(S-Post+DMSO组)。采用结扎左冠状动脉前降支30 min再灌注120 min的方法制备大鼠心肌缺血再灌注损伤模型。S组只穿线不结扎,S-Post组于再灌注前10 min时吸入2.5%七氟醚15 min;S-Post+5-HD组和S-Post+DMSO组于再灌注前10 min时分别尾静脉注射5-羟基癸酸5 mg/kg和等容量二甲基亚砜,余处理同S-Post组。再灌注120 min时取心肌组织,光镜下观察病理学结果,电镜下观察心肌细胞线粒体超微结构,采用免疫组化法和RT-PCR法检测Drp1及其mRNA表达水平。结果与S组比较,I/R组、S-Post组、S-Post+5-HD组和S-Post+DMSO组心肌Drp1及其mRNA表达上调(P<0.05),心肌病理学损伤明显;与I/R组比较,S-Post组和S-Post+DMSO组心肌Drp1及其mRNA表达下调(P<0.05),心肌病理学损伤减轻,S-Post+5-HD组上述指标差异无统计学意义(P>0.05);与S-Post组比较,S-Post+5-HD组心肌Drp1及其mRNA表达上调(P<0.05),心肌病理学损伤加重,S-Post+DMSO组上述指标差异无统计学意义(P>0.05)。结论七氟醚后处理可通过开放心肌mito-KATP通道,进而下调Drp1表达,减轻大鼠心肌缺血再灌注损伤。Objective To investigate the relationship between dynamin-related protein 1(Drp1)and mitohondrial KATP(mito-KATP)channel during sevoflurane postconditioning-induced reduction of myocardial ischemia-reperfusion(I/R)injury in rats.Methods Forty clean-grade healthy adult male Sprague-Dawley rats,weighing 220-280 g,were divided into 5 groups(n=8 each)according to a random number table method:sham operation group(group S),myocardial I/R group(group I/R),sevoflurane postconditioning group(group S-Post),sevoflurane postconditioning plus 5 hydroxydecanoic acid(5-HD)group(group S-Post+5-HD)and sevoflurane postconditioning plus dimethyl sulfoxide group(group S-Post+DMSO).Myocardial I/R was induced by 30-min occlusion of left anterior descending branch of the coronary artery followed by 120-min reperfusion in anesthetized rats.The left anterior descending branch of coronary artery was only occluded but not ligated in group S.The rats inhaled 2.5%sevoflurane for 15 min starting from 10 min before reperfusion in group S-Post.In S-Post+5-HD and S-Post+DMSO groups,5-HD 5 mg/kg and the equal volume of dimethyl sulfoxide(DMSO)were injected via the caudal vein at 10 min before reperfusion,respectively,and the other treatments were similar to those previously described in group S-Post.The myocardial specimens were taken at 120 min of reperfusion for examination of the pathological changes(with a light microscope)and ultrastructure of myocardial cells(by electron microscopy),and for determination of the expression of Drp-1 protein(by immunohistochemistry)and mRNA(by real-time polymerase chain reaction).Results Compared with group S,the expression of myocardial Drp-1 protein and mRNA was significantly up-regulated(P<0.05),and the pathologic changes were significantly attenuated in I/R,S-Post,S-Post+5-HD and S-Post+DMSO groups.Compared with group I/R,the expression of myocardial Drp-1 protein and mRNA was significantly down-regulated,and the pathologic changes were significantly attenuated in S-Post and S-Post+DMSO groups,and no signi

关 键 词：麻醉药 吸入 心肌再灌注损伤 线粒体蛋白质类 后处理 KATP通道 

分 类 号：R614[医药卫生—麻醉学]