伊伐布雷定对慢性心力衰竭伴室性心律失常兔模型HCN通道的影响  

Effect of Ivabradine on HCN channels in rabbit models with chronic heart failure companying ventricular arrhythmia

作　　者：吴婷玉[1] 周景芬[1] WU Ting-yu;ZHOU Jing-fen(Department of Geriatrics,Wuhan No.1Hospital in Hubei Province,Wuhan 430022,China)

机构地区：[1]武汉市第一医院老年病科

出　　处：《中国心血管病研究》2018年第12期1138-1143,共6页Chinese Journal of Cardiovascular Research

基　　金：湖北省卫生和计划生育委员会科研项目(项目编号:wj2017f012)

摘　　要：目的 观察伊伐布雷定对慢性心力衰竭伴室性心率失常兔模型超级化激活环核苷酸门控阳离子通道(HCN)的影响.方法 纳入由华中科技大学同济医学院实验动物中心提供的80只健康成年大白兔为研究对象,随机分为正常对照组(20只,予以0.9%生理盐水)和慢性心力衰竭组(60只,经耳缘静注异丙肾上腺素0.3 mg·kg-1·d-1).待慢性心衰组造模满意后将BW-200生理无线遥测心电系统芯片植入兔皮下,将其分为模型组(30只,0.9%生理盐水,洗胃,持续2周)和伊伐布雷定组(30只,伊伐布雷定7 mg·kg-1·d-1,持续2周).分别于起搏前(0周)、起搏4周、6周(药物干预2周后),观察四组心率(HR)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、心室有效不应期(ERP)、ERP离散度(dERP)、室性心律失常(VA)诱发率、心室颤动阈值(VFT)变化,并分析HCN2、HCN4通道表达水平.结果起搏4、6周后,慢性心力衰竭组HR、LVEDD、LVESD、ERP、dERP、VA诱发率均显著高于起搏前及正常对照组(P<0.05),LVEF显著低于起搏前及正常对照组(P<0.05);其中,起搏4周后,伊伐布雷定组HR、LVEDD、LVESD、LVEF、ERP、dERP、VFT较模型组均未见统计学差异(P>0.05);起搏6周后,伊伐布雷定组HR、LVEDD、ERP、VA诱发率显著低于模型组(P<0.05),VFT显著高于模型组(P<0.05),但LVESD、LVEF、dERP较模型组均未见统计学差异(P>0.05).慢性心力衰竭组HCN2通道和HCN4通道的mRNA、microRNA-1、microRNA-133及蛋白表达水平均显著高于正常对照组(P<0.05);其中,伊伐布雷定组上述指标均显著低于模型组(P<0.05).结论 伊伐布雷定能有效降低慢性心力衰竭兔心率,缩短ERP值,诱导慢性心力衰竭兔室性心律失常诱发率下降,改善心室颤动阈值,并降低慢性心力衰竭兔心室肌HCN2通道和HCN4通道表达水平,有助于指导慢性心力衰竭伴室性心率失常临床治疗.Objective In order to observe the effect of Ivabradine on super activated cyclic nncleotide gated cation channel (HCN)in rabbits with chronic heart failure companying ventricular arrhythmia.Methods The 80healthy adult white rabbits provided by experimental animal center of Tongji Medical College of Huazhong University of Science and Technology were randomly divided into normal control group (20rats,0.9% physiological saline)and chronic heart failure group (60with Isoproterenol 0.3mg·kg^-1·d^-1).After the chronic heart failure group was satisfied,the BW-200physiological radio telemetering ECG system was implanted under the rabbit skin and divided into the model group (30,0.9%saline,gastric lavage,2weeks)and the Ivabradine group (30,Ivabradine 7mg·kg^-1·d^-1for 2weeks).Respectively (0weeks)before the pacemaker,pacemaker 4 weeks,6weeks (2weeks after the drug intervention),the four groups of heart rate (HR),left ventricular end-diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD),left ventricular ejection fraction (LVEF),ventricular effective refractory period (ERP),ERP discrete degree (dERP)and ventricular arrhythmia (VA)induced rate and ventricular fibrillation threshold (VFT)changes were observed and the engineered HCN2 and HCN4channel expression level were analyed.Results After 4and 6weeks of pacing,the rates of HR, LVEDD,LVESD,ERP,dERP and VA in the chronic heart failure group were significantly higher than those before and in the normal control group (P<0.05);and the LVEF was significantly lower than that before and in the normal control group (P<0.05).After 4weeks pacing,the HR,LVEDD,LVESD,LVEF,ERP,dERP and VFT in the Ivabradine group were not statistically significant compared with the model group (P>0.05).After 6 weeks of pacing,the HR,LVEDD,ERP and VA induction rate of in the Ivabradine group was significantly lower than that in the model group (P<0.05);and the VFT was significantly higher than that in the model group (P< 0.05);but LVESD,LVEF and dERP were not statistically signific

关 键 词：伊伐布雷定 慢性心力衰竭 室性心率失常 兔模型 环核苷酸门控阳离子通道 

分 类 号：Q95-33[生物学—动物学] R5416[医药卫生—心血管疾病]