参仙升脉的心电生理作用及其增快窦房结自主心率机制的研究  

Electrophysiological Effects of Shenxian Shengmai and Mechanisms Underlying the Increase of Intrinsic Sinus Rate of the Heart

作　　者：陈英 黄郁文 王春华 王程瑜 林明杰 朱彦 赵步长 吴林[1] CHEN Ying;HUANG Yuwen;WANG Chunhua;WANG Chenyu;LIN Mingjie;ZHU Yan;ZHAO Buchang;WU Lin(Department of Cardiology,Peking University First Hospital,Beijing(100034),China)

机构地区：[1]北京大学第一医院心内科,北京市100034 [2]天津中医药大学中药制药工程学院 [3]天津国际生物医药研究院中药研发中心 [4]西安步长心脑血管病医院

出　　处：《中国循环杂志》2021年第9期897-902,共6页Chinese Circulation Journal

基　　金：国家自然科学基金(81770325)。

摘　　要：目的:探索参仙升脉口服液萃取剂参仙升脉(SXSM)增快窦房结自主心率的机制及其对房室结、心房和冠状动脉血流的影响。方法:采用雄性Hartley豚鼠58只行Langendorff离体心脏灌流实验。根据给药的不同,随机将46只豚鼠离体心脏分为SXSM组(n=22,10只测量自主心率和心电图指标,6只测量房室结传导指标,6只测量心房电生理指标和冠状动脉导流率),异丙肾上腺素组(n=6),乙酰胆碱组(n=6),SXSM(1.00 ml/L)+乙酰胆碱预防组(n=6)和乙酰胆碱(3.00μmol/L)+SXSM治疗组(n=6),观察不同分组给药前后的窦房结固有心率和各项心电生理指标及冠状动脉灌注压的变化。余12只灌流实验结束后分别收集给予乙酰胆碱(n=4)、乙酰胆碱+SXSM(n=4)及不给药(n=4)心脏的心房组织,通过蛋白免疫印迹法测定乙酰胆碱M2受体(mAChR2)蛋白的相对表达水平。结果:SXSM浓度依赖性增快心率,延长房室结传导时间,缩短心房动作电位时程与有效不应期,并增大冠状动脉导流率(P均<0.05),但与异丙肾上腺素相比升高心率的幅度低[(24.2±5.3)次/min vs.(117.0±26.0)次/min,P<0.05],延长房室结传导时间(P<0.05);与乙酰胆碱组相比,SXSM(1.00 ml/L)+乙酰胆碱预防组致心动过缓的量效曲线右移(4.1±1.7)倍(P<0.05);SXSM浓度依赖性增快乙酰胆碱(3.00μmol/L)处理后的心率,心率增加幅度高于SXSM组[(67.4±25.0)次/min vs.(24.2±5.3)次/min,P<0.05];SXSM(1.00 ml/L)可逆转乙酰胆碱(3.00μmol/L)引起的心房组织mAChR2蛋白表达水平的增高[(51.0±11.0)%vs.(138.0±44.0)%,P<0.05]。结论:SXSM增加自主心率,延长房室结传导时间,缩短心房有效不应期和动作电位时程,增加冠状动脉血流。SXSM对迷走神经活动增高引起的心动过缓有预防和治疗作用,其增快心率的机制可能与拮抗mAChR2有关。Objectives:To explore the mechanisms of Shenxian Shengmai Oral Liquid extract-SXSM in increasing the intrinsic heart rate of sinoatrial node and its effects on atrioventricular nodal conduction,atrial electrophysiological parameters and coronary conductance rate.Methods:Fifty-eight male Hartley guinea pigs were used in the Langendorff perfusion heart experiments,of which 12 were used in the western blot experiments.According to different administration,guinea pig hearts were randomly divided into SXSM group(n=22,of which 10,6 and 6 were used to measure atrial rate and electrocardiographic parameters,atrioventricular nodal conduction parameters,atrial electrophysiological parameters and coronary conductance rate,respectively),isoproterenol group(n=6),acetylcholine group(n=6),SXSM(1.00 ml/L)plus acetylcholine group(n=6)and acetylcholine(3.00μmol/L)plus SXSM group(n=6).The changes of intrinsic heart rate of sinoatrial node,various electrophysiological parameters and coronary perfusion pressure before and after administration in different groups were observed.At the end of experiments,atrial tissue was collected from heats of either control or treated with acetylcholine in absence and presence of SXSM(n=4 in each group).The relative expression levels of acetylcholine M2 receptor protein were determined using western blot.Results:SXSM concentration-dependently increased intrinsic heart rate,prolonged atrioventricular nodal conduction time,shortened atrial action potential duration and effective refractory period,and increased coronary conductance rate(P<0.05,n=6-10),while isoproterenol caused a greater increase in heart rate compared with SXSM([117.0±26.0]bpm vs.[24.2±5.3]bpm,P<0.05)and shortened atrioventricular nodal conduction time.Compared with the acetylcholine group,the concentration-response curve of bradycardia in the SXSM(1.00 ml/L)plus acetylcholine group shifted to the right by(4.1±1.7)times(P<0.05).SXSM increased the heart rate after acetylcholine(3.00μmol/L)pretreated in a concentrationdependent mann

关 键 词：参仙升脉 窦房结功能不全 电生理机制 乙酰胆碱 迷走神经活动 

分 类 号：R541.4[医药卫生—心血管疾病]