右美托咪定对快速心房起搏后兔心房电生理学特性及Cx43 Cx40表达的影响

Effects of dexmedetomidine on atrial electrophysiological characteristics and expression of Cx43 and Cx40 in rabbits after rapid atrial pacing

目的探讨右美托咪定对快速心房起搏后兔心房电生理学特性及Cx43、Cx40表达的影响。方法选择成年雄兔24只,随机分为对照组(C组)、快速心房起搏组(RAP组)与快速心房起搏+右美托咪定灌流组(RAP+DEX组),每组8只。制备Langendorff离体心脏灌注模型,通过快速心房起搏构建房颤模型。分别检测3组心房90%单相动作电位复极时程(MAPD 90)、心房有效不应期(ERP)、ERP与MAPD 90比值(ERP/MAPD 90)、房颤诱发率及持续时间,取心房组织,采用Western-bolt法和免疫荧光法检测Cx43、Cx40的蛋白含量和分布。结果T 1~T 3时,3组MAPD 90比较,差异有统计学意义(P<0.05)。RAP组MAPD 90随时间的推移有逐渐下降趋势(P<0.05),不同的处理方式和时间对MAPD 90有交互作用(P<0.05)。T 3时,RAP组ERP、ERP/MAPD 90、Cx43和Cx40蛋白含量均低于C组和RAP+DEX组,房颤诱发率高于C组和RAP+DEX组,差异有统计学意义(P<0.05)。3组房颤持续时间比较,差异无统计学意义(P>0.05)。电镜下,RAP组Cx43和Cx40分布不规律且侧面分布增多,而C组和RAP+DEX组Cx43和Cx40分布较规律且主要集中在两端。结论右美托咪定可抑制房颤时的心房电重构,降低房颤的易感性,其机制可能与其抑制Cx43、Cx40的表达下调和再分布有关。

Objective To investigate the effects of dexmedetomidine on atrial electrophysiological characteristics and Cx43 and Cx40 expression in rabbits after rapid atrial pacing.Methods Twenty-four adult male rabbits were selected and randomly divided into three groups:control group(Group C),rapid atrial pacing group(group RAP),and rapid atrial pacing+dexmedetomidine perfusion group(group RAP+DEX),with 8 rabbits in each group.Langendorff in vitro perfusion model was prepared,and atrial fibrillation model was established by rapid atrial pacing.The atrial monophasic action potentials after 90%calendar(MAPD 90),the effective refractory period(ERP),the ratio of ERP to MAPD 90(ERP/MAPD 90),and the induction rate and duration of atrial fibrillation in three groups were measured respectively.Finally,the protein content and distribution of Cx43 and Cx40 were detected by Western bolt and immunofluorescence method in the atrium tissues.Results At T 1~T 3,MAPD 90 was compared among the three groups,and the difference was statistically significant(P<0.05).MAPD 90 in group RAP showed a gradual downward trend over time,and different treatment methods and time had interaction effects on MAPD 90(P<0.05).At T 3,the content of ERP,ERP/MAPD 90,Cx43 and Cx40 in group RAP was lower than that in group C and group RAP+DEX,and the incidence of atrial fibrillation was higher than that in group C and group RAP+DEX(P<0.05).There was no significant difference in duration of atrial fibrillation among three groups(P>0.05).Under electron microscope,the distribution of Cx43 and Cx40 in group RAP was irregular and increased from the side,while the distribution of Cx43 and Cx40 in group C and group RAP+DEX was regular and mainly concentrated at both ends.Conclusion Dexmedetomidine can inhibit the atrial electrical remodeling in atrial fibrillation and reduce the susceptibility to atrial fibrillation.The mechanism may be related to the down-regulation and redistribution of Cx43 and Cx40.