异氟烷对心肌动作电位及缝隙连接蛋白Cx43的作用

Effects of Isoflurane on Action Potential of Heart and Expression of Myocardial Connexin 43

目的:观察异氟烷对心肌动作电位及缝隙连接蛋白Cx43表达的影响。方法:健康家兔40只,采用Langendorff离体心脏平衡灌注15 min后,随机分为5组:I0.65组,用0.65 MAC异氟烷的K-H液灌注;I0.65H用0.65MAC异氟烷加0.5 mmol/L庚醇的K-H液灌注;I1.3组,用1.3 MAC异氟烷的K-H液灌注;H0.5组,用庚醇0.5 mmol/L的K-H液灌注;S组,用K-H液灌注。观察记录灌流15 min时(基础值)和给药15 min时的心率(HR)及心内膜心肌(Endo)、中层心肌(M)、心外膜心肌(Epi)的动作电位时程(APD)和振幅(APA),灌注完毕取左心室心肌组织,用免疫组织化学检测心肌Cx43蛋白表达。结果:I0.65组心肌动作电位无明显影响,I1.3组APD显著延长(P<0.05),H0.5组HR显著减慢(P<0.05),APD显著延长(P<0.05),I0.65H组给药后有发生心律失常甚至心电活动停止现象;Cx43蛋白表达I0.65H组较H0.5组表达少(P<0.05),H0.5组较I0.65、I1.3组表达少(P<0.05),I1.3组较I0.65组、S组表达少(P<0.05)。结论:异氟烷与庚醇对心脏动作电位和缝隙连接蛋白Cx43可能有着相似的作用,延长动作单位时程,减少Cx43蛋白表达,改变Cx43蛋白分布;异氟烷可能通过阻滞缝隙连接,对心脏动作电位产生作用。

Objective： To observe the effects of isoflurane on action potential（AP） of heart and the expression of myocardial connexin43（Cx43）.Methods： Forty isolated rabbit hearts were perfused for 15 minutes with modified Krebs-Hensleit buffer using Langendorff device.Then,all the hearts were randomly divided into five groups（n=8 in each）： group I0.65,group I0.65H,group I1.3,group H0.5 and group S,in which hearts were perfused with Kreb-Hensleit buffer containing 0.65 MAC isoflurane,0.65 MAC isoflurane plus 0.5 mmol/L heptanol,1.3 MAC isoflurane,0.5 mmol/L heptanol and Kreb-Hensleit buffer only respectively.Heart rates（HR）,AP course（APD） and AP amplitude（APA） of endocardium（Endo）,mid-layer myocardium（M） and epicardium（Epi） were recorded before and after medication.Left ventricular myocardial tissues were then taken.The expression of myocardial Cx43 protein was detected with immunohistochemistry method.Results： AP didn＇t change significantly in group I0.65,while APD lengthened in group I1.3（P0.05）,HR slowed down（P0.05） and APD lengthened in group H0.5.Arrhythmia occurred or even electricity activity stopped in group I0.65H.The expression of Cx43 protein in group I0.65H was less than that in group H0.5（P0.05）.The expression of Cx43 protein in group H0.5 was less than those in group I0.65 and group I1.3（P0.05）.The expression of Cx43 protein in group I1.3 was less than those in group I0.65 and group S.（P0.05）.Conclusions： Isoflurane and heptanol may have similar effects on AP and the expression of Cx43 in heart.They lengthen APD,reduce the expression of Cx43 protein,change its distribution.Isoflurane may affect AP of heart through changing the content and the distribution of Cx43.