淫羊藿苷对兔充血性心力衰竭引起室性心律失常的影响及其电生理机制-《中国医学物理学杂志》

文章信息/Info

Title:: Effects of icariin on ventricular arrhythmia induced by congestive heart failure in rabbit in vivo and its electrophysiological mechanisms

文章编号:: 1005-202X（2020）03-0361-07

作者:: 汪晶晶; 董蔚; 蒋博; 李丹丹; 张威; 王晶; 穆洋; 陈思; 李泱; 陈韵岱; 中国人民解放军总医院第一医学中心心血管内科，北京 100853

Author(s):: WANG Jingjing; DONG Wei; JIANG Bo; LI Dandan; ZHANG Wei; WANG Jing; MU Yang; CHEN Si; LI Yang; CHEN Yundai; Department of Cardiology, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China

关键词:: 充血性心力衰竭; 淫羊藿苷; 室性心律失常; L-型钙电流

Keywords:: Keywords: congestive heart failure; icariin; ventricular arrhythmia; L-type calcium current

分类号:: R331.31

DOI:: DOI:10.3969/j.issn.1005-202X.2020.03.020

文献标志码:: A

摘要:: 目的：探讨淫羊藿苷（ICA）对家兔充血性心力衰竭（CHF）引起室性心律失常的影响及其电生理机制。方法：实验分为对照组、CHF组和CHF+ICA组（ICA组），采用雄性新西兰大耳白兔。CHF模型制备是经兔耳缘静脉注射异丙肾上腺素（0.3 mg/kg/d，连续注射3周）诱导，然后继续喂养并观察临床指征、M型超声心动图指标中左心室射血分数及短轴缩短率和Ⅱ导心动图的心率、QT间期等主要参数变化以确定CHF模型成功。利用记录在体心室肌单相动作电位和程控电刺激技术以及短阵快速刺激方法观察各组动作电位的最大上升速率（Maxdv/dt）和复极化到20%、50%和90%时程（APD20、APD50、APD90）等主要参数以及基础刺激周长为150 ms时心室有效不应期（ERP150）及其离散度（dERP150）和室性心律失常诱发周期及其诱发率。酶解法分离单个心室肌细胞，全细胞膜片钳技术记录心室肌细胞L-型钙电流（ICa-L）及其电流-电压（I-V）曲线。结果：当入选制造模型的兔出现消瘦、无力、气促和肌肉萎缩等临床症状，心室射血分数和短轴缩短率均明显减小，左心室腔明显扩大，室间隔显著变薄（P均<0.01），心率减慢（P<0.05），PR和QT间期均显著延长（P<0.01），ST段明显上移（P<0.05），提示CHF模型制造成功。与CHF组比较，经ICA治疗的兔心室肌组织的动作电位幅度明显增加，Maxdv/dt加快，APD10、APD20、APD50和APD90均明显缩短（P均<0.01）。另外，ICA组的CHF兔的心室肌组织ERP150及其离散度dERP150以及被诱发室性心律失常的基础刺激周长明显缩短，室性心律失常诱发率显著减少（P<0.01）。最后，经电压钳制，在ICA作用下，CHF心室肌细胞ICa-L明显减小，I-V曲线显著上抬，当钳制电压为+10 mV时，经ICA治疗的CHF兔心室肌细胞ICa-L峰值大小由原CHF组心室肌细胞ICa-L电流密度的（9.98±0.53） pA/pF减小为（6.95±0.15） pA/pF（P<0.01）。结论：ICA能够明显改善家兔CHF引起的心室电重构，降低CHF心脏对室性心律失常的易感性，起到抗CHF引起的室性心律失常作用，其机制可能是ICA能显著抑制CHF心室肌细胞ICa-L，防治CHF心室肌细胞内Ca2+超载和Ca2+振荡。

Abstract:: Abstract: Objective To investigate the effects of icariin (ICA) on ventricular arrhythmias (VA) induced by congestive heart failure (CHF) in rabbits in vivo and discuss its electrophysiological mechanism. Methods Healthy New Zealand male rabbits were divided into 3 groups, namely control group, CHF group and CHF+ICA group (ICA group). The CHF models were induced by isoproterenol injection (0.3 mg/kg/d for 3 weeks) via the ear vein; and whether the CHF models were established successfully was determined by clinical symptoms, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in M-type echocardiogram, and heart rate and QT interval in Ⅱ-lead electrocardiogram (ECG). Some main electrophysiological parameters in 3 groups were recorded, such as maximum upstroke velocity (Maxdv/dt) of action potential, action potential duration at 20%, 50% and 90% repolarization (APD20, APD50 and APD90) from the recording of monophasic action potential (MAP) of ventricular muscle, and the ventricular effective refractory period (ERP150) with 150 ms of basic cycle length detected by programmed electrical stimulation and its dispersion (dERP150), and the inducibility and duration of VA detected by Burst-pacing. The L-type calcium current (ICa-L) and its current-voltage (I-V) curve were recorded by whole-cell patch clamp technique in enzymatically dissociated single ventricular myocyte in 3 groups. Results When the rabbits for the establishment of CHF model presented with clinical symptoms, such as emaciation, weakness, tachypnea, and muscle atrophy, and the LVEF and LVFS of the rabbits were obviously decreased, and left?ventricular?end-diastolic?internal?diameter was enlarged as well as interventricular septal thickness at diastole was attenuated (all P<0.01), and heart rate significantly dropped (P<0.05), and PR and QT interval were markedly lengthened (all P<0.01), and ST segment was upward (P<0.05), it was suggested that the CHF models were established successfully. Compared with CHF group, the administration of ICA not only significantly increased the action potential amplitude of ventricular tissues and Maxdv/dt, but also shorten APD10, APD20, APD50 and APD90 (all P<0.01). Moreover, the ERP150 and dERP150 of ventricular tissues as well as basic cycle length of induced VA were notably shortened. The induction rate of VA was significantly decreased with the administration of ICA (P<0.01). Finally, with voltage clamp, the administration of ICA markedly decreased the ICa-L of ventricular myocytes in CHF models, and upward I-V curve; and when the clamping voltage was +10 mV, the peak value of ICa-L of ventricular myocytes were significantly decreased from (9.98±0.53) pA/pF in CHF group to (6.95±0.15) pA/pF in ICA group (P<0.01). Conclusion ICA might notably modify the electrical remodeling and decrease the susceptibility to VA induced by CHF, therefore realizing anti-ventricular arrhythmias in CHF rabbits. The mechanisms might attribute to that ICA can markedly decrease ICa-L, and prevent calcium overload and oscillations with ICA perfusion in ventricular myocytes of CHF rabbits.

《中国医学物理学杂志》[ISSN:1005-202X/CN:44-1351/R]

文章信息/Info

备注/Memo

常用功能

导航/Navigate

工具/Tools

统计/Statistics