雷诺嗪对大鼠急性心肌梗死早期心室肌缝隙连接蛋白43的影响  

The effects of ranolazine on connexin 43 of rat following acute myocardial infarction

作　　者：郑展雄 张祥宇 江力勤 张冉 ZHENG Zhanxiong;ZHANG Xiangyu;JIANG Liqin;ZHANG Ran(Department of Cardiology,The Seconed Hospital of Jiaxing,Jiaxing 314000,China)

机构地区：[1]嘉兴市第二医院心内科,314000

出　　处：《心电与循环》2020年第4期333-337,I0002,共6页Journal of Electrocardiology and Circulation

基　　金：嘉兴市科技计划(2017AY33032)。

摘　　要：目的观察雷诺嗪对急性心肌梗死早期心室肌缝隙连接蛋白43(Cx43)细胞表面分布、磷酸化及表达总量的影响。方法50只雄性SD大鼠随机分为:假手术组,对照组,雷诺嗪低浓度组、中浓度组和高浓度组,每组各10只。假手术组和对照组经尾静脉注射0.9%氯化钠溶液,雷诺嗪低、中、高浓度组分别注射雷诺嗪0.05mg/kg,0.5mg/kg和5mg/kg。给药10min后,对照组和雷诺嗪组结扎冠状动脉左前降支。记录2 h心电图,随后处死大鼠获取心脏标本,比色法测心肌细胞内钙离子浓度,免疫荧光染色检测梗死区Cx43表达量,观察细胞表面Cx43分布,Western blot法测p-Cx43总量。结果与对照组比较,雷诺嗪组快速性室性心律失常评分降低(P<0.05),Tp-e/Q-Tc比值降低,Tp-e间期、Q-Tc间期缩短(均P<0.05),心肌细胞内钙离子浓度降低(P<0.05),Cx43、p-Cx43的降解减慢(均P<0.05),Cx43细胞表面分布侧面化减少。结论雷诺嗪可降低大鼠急性心肌梗死早期室性心律失常的发生率,减缓Cx43的降解,减轻Cx43的细胞分布侧面化。这种作用可能与雷诺嗪阻滞晚钠电流,降低心肌细胞内钙离子浓度,稳定Cx43和钠离子通道蛋白连接相关。Objective To observe the effects of ranolazine on connexin 43(Cx43)of rat following acute myocardial infarction.Methods 50 male SD rats were randomly divided into shame operation group(n=10),control group(n=10)and ranolazine group(n=30).Saline was injected via tail veil in shame operation group and control group.Ranolazine group was divided into three groups and injected with ranolazine at dose of 0.05 mg/kg,0.5 mg/kg and 5 mg/kg,respectively.Left anterior descending coronary artery was ligated 10 min later after injection and then 2-hours electrocardiogram was recorded.At last,the rats were sacrificed and cardiac samples were collected.The intramyocyte calcium concentration,the expression of Cx43 in infarction area,the distribution of Cx43 over the cell surface and the total of p-Cx43 were measured.Results Compared with control group,ranolazine reduced the scores of ventricular tachyarrhythmias(P<0.05),Tp-e/Q-Tc ratio,the Tp-e interval and Q-Tc interval(all P<0.05).The intramyocyte calcium concentration decreased.The degradation of Cx43 and p-Cx43 was delayed(all P<0.05).The laterally dispersed Cx43 over the cell surface was reduced.Conclusion Ranolazine may decrease the incidence of ventricular tachyarrhythmias of rats with acute myocardial infarction,delay the degradation of Cx43 and reduce the lateralization of Cx43.This effects may be depended on ranolazine block the late sodium current,reduce the concentration of[Ca2+],stabled Cx43 connection with sodium-ions channel protein.

关 键 词：雷诺嗪 大鼠 急性心肌梗死 缝隙连接蛋白43 磷酸化缝隙连接蛋白43 

分 类 号：R965[医药卫生—药理学]