老龄化对家兔左心房心律失常发生的电生理特征影响  

Effects of Aging on Electrophysiological Properties in Aging-Related Left Atrium Arrhythmogenesis in Rabbits

作　　者：杨淑红[1,2] 王凤秀[1,2,3] 吴平亚 杨峥[1,2] 吴成云[1,2] 李文星[1,2] 徐辉文[1,2,5] 

机构地区：[1]武汉大学人民医院外科门诊 [2]武汉大学心血管病研究所,湖北武汉430060 [3]北京信息职业技术学院医学门诊部,北京100200 [4]武汉市洪山区张家湾街社区卫生服务中心,湖北武汉430065 [5]武汉大学人民医院老年科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2015年第5期685-689,共5页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2011CDB504);湖北省卫生计生科研基金资助项目(编号:JX6B67)

摘　　要：目的:探讨老龄化易于家兔左心房(LA)心律失常发生的电生理特征及其机制。方法:实验由青龄兔[年龄6个月,分为青龄对照组(青龄组)和青龄+异丙肾上腺素(ISO)组(青龄药物组)]和老龄兔[年龄26个月,分为老龄对照组(老龄组)和老龄+ISO组(老龄药物组)]雄性新西兰大耳白兔参与。利用常规微电极记录LA组织的跨膜动作电位(tAP),观察静息膜电位(RMP)、动作电位幅度(APA)、动作电位最大上升速率(Vmax)、动作电位复极化到20%和50%以及90%时程(APD20、APD50、APD90)以及延迟后除极(DADs),酶解法分离单个LA细胞,全细胞膜片钳技术记录LA细胞L-型钙电流(ICa-L)在使用ISO前后反应。结果:与青龄组比较,老龄组动作电位形态明显增宽,传导减慢,APD20、APD50和APD90均显著延长,APA、Vmax和RMP都明显减少或降低(P<0.05或0.01);在ISO作用下,青龄和老龄药物组tAP都明显变窄,传导增快,但与青龄药物组比较,老龄药物组APD各值缩短更加明显,APA、Vmax、RMP幅度都显著增大(P均<0.05),动作电位之后出现更大幅度的延迟后除极(DADs);在电压钳制方式下,与青龄组比较,老龄组ICa-L均明显减少,当钳制电压为+10mV时,老龄组ICa-L电流密度由青龄组的(9.5±1.3)pA/pF减少为(6.3±0.8)pA/pF(P<0.01),老龄组ICa-L的电流-电压(I-V)曲线明显上抬。在ISO作用下,青龄和老龄药物组ICa-L电流密度均明显高于各自对照组(P<0.01),但与青龄药物组比较,老龄药物组ICa-L电流密度增加更加明显(P<0.05),老龄药物组ICa-L的I-V处于其他各组LA细胞ICa-L的I-V曲线最下部。结论:老龄化LAs电生理特性在ISO的作用前后均发生了明显电重构,它为折返和触发性房性心律失常发生提供了易损条件和病理生理基础,其电生理机制是老龄LA细胞ICa-L在ISO干扰前后发生离子通道重构,引发细胞内Ca2+异常调控,使老龄化房性心律失常具有非常显著的易感性。Objective. To investigate electrophysiological properties and mechanism of aging to facilitate left atrium （LA） arrhythmogenesis in rabbits. Methods： The male New Zealand rabbits were divide into young （age, 6 months） and aged （age, 26 months） groups. According to the comparion before and after isoproterenol （ISO） administration, young rabbits were further divided into young control （young group） and young ＋ ISO group （young medicine group）, and aged rabbits were also divided into aged control （aged group） and aging ＋ ISO group （aged medicine group）. Electrophysiological study was performed on perfused isolated LA preparations by using conventional microelectrodes to record the transmenbrane action potentials （tAP）, so that determined RMP, APA, V APD20 ,APD50, APDg0 as well as delayed afterdepolarizations （DADs） before and after the administration of ISO in rabbit LA tissue specimens. L-type calcium current （Ica-L） was recorded via whole-cell patch clamp technique in enzymatically dissociated single rabbit LA myocytes before and after the drug administration. Results： Compared with young group, studies on the tAP of aged rabbit LAs showed that the tAP contour became obviously widened, and the tAP conduction slowed down. And the APD20, APD50 and APD90 were significantly longer, and APA, Vmax and RMP obviously decreased in aged group （P of all 〈0.05 or 0.01, respectively）. Otherwise, the tAP contour changed narrow and conduction of tAP was fast as well as was induced many DADs both young and aged medicine group. However, difference with main parameters of young medicine group, the values of APD were obviously shorten, and APA, V RMP and DADs amplitude were significantly increased in aged medicine group （P of all 〈0.05, respectively）. With voltage clamp model, the current density of Ica-L was significantly decrease from （9.5±1.3） pA/pF in young group to （6.3±0.8） pA/pF in aged group under ＋10 mV clamp voltage （P〈0.01）, and the current-

关 键 词：老年性左心房 跨膜动作电位 离子通道 电重构 心律失常易感性 

分 类 号：R541.75[医药卫生—心血管疾病] R592[医药卫生—内科学]