β_(1)肾上腺素受体自身抗体激活对心室空间电生理特性的影响及其干预研究  

The Effect ofβ_(1)-Adrenergic Receptor Autoantibodies Activation on Electrophysiological Properties of Ventricular Space and Its Intervention

作　　者：杨娜 汤宝鹏[1] 孙华鑫 喜林强 商鲁翔 王倩辉 迪拉热·太外库力 宋洁 周贤惠[1] YANG Na;TANG Baopeng;SUN Huaxin;XI Linqiang;SHANG Luxiang;WANG Qianhui;Dilare·Taiwaikuli;SONG Jie;ZHOU Xianhui(Department of Pacing Electrophysiology,Cardiac Centre,The First Affiliated Hospital of Xinjiang Medical University,Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling,Urumqi 830054,Xinjiang,China;Department of Cardiology,The Affiliated Hospital of Southwest Jiaotong University,The Third People’s Hospital of Chengdu,Cardiovascular Disease Research Institute of Chengdu,Chengdu 610031,Sichuan,China;Department of Cardiology,The First Affiliated Hospital of Shandong First Medical University(Shandong Province Thousand Buddhas Hospital),Shandong Provincial Key Laboratory of Medical and Health Arrhythmias,Jinan 250014,Shandong,China)

机构地区：[1]新疆医科大学第一附属医院心脏中心起搏电生理科新疆心电生理与心脏重塑重点实验室,新疆乌鲁木齐830054 [2]西南交通大学附属医院成都市第三人民医院心内科成都市心血管病研究所,四川成都610031 [3]山东第一医科大学第一附属医院(山东省千佛山医院)心内科山东省医药卫生心律失常重点实验室,山东济南250014

出　　处：《心血管病学进展》2024年第7期654-660,共7页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(82100343,82260065,82260064,82060069);代谢紊乱相关心血管疾病北京市重点实验室基金(DXWL2022-04);新疆维吾尔自治区研究生科研创新项目资助(XJ2023G168)。

摘　　要：目的室性心律失常的发生与β_(1)肾上腺素受体自身抗体(β_(1)AAbs)有关。本研究旨在探讨β_(1)AAbs对大鼠心室空间电生理特性的作用及干预效果。方法将30只6~8周龄雄性SD大鼠(体重180~220 g)随机分为3组(每组n=10):对照组、β_(1)AAbs组和比索洛尔组。在0、2、4、6周经背部多点注射β_(1)肾上腺素受体第二细胞外环抗原肽建立主动免疫室性心律失常易感模型。测定不同时间节点的血清β_(1)AAbs水平验证模型。在心室不同区域测量电生理参数心室有效不应期、有效不应期离散度、传导速度和传导异质性。马松染色检测心室组织不同区域的纤维化水平。结果与对照组相比,β_(1)AAbs组与比索洛尔组自第2~8周β_(1)AAbs水平显著增高(P<0.05)。与对照组和比索洛尔组相比,β_(1)AAbs组的心率显著增加,RR间期、QT间期和QTc间期明显缩短(P<0.05);不同区域心室有效不应期均明显缩短,有效不应期离散度显著增加(P<0.05),不同区域传导速度减慢、传导异质性增加(P<0.05),不同部位胶原容积百分比明显升高(P<0.05),以上参数改变在中间部最为明显,均可被比索洛尔逆转(P<0.05)。结论β_(1)AAbs可增加心室空间电生理特性改变,其潜在机制可能与不同区域纤维化程度有关,比索洛尔具有潜在治疗价值。Objective The occurrence of ventricular arrhythmias has been associated with theβ_(1)-adrenergic receptor autoantibodies(β_(1)AAbs).The aim of this study was to investigate the role ofβ_(1)AAbs on the electrophysiological properties of rat ventricular space and its intervention.Methods Thirty male SD rats aged 6 to 8 weeks(weighing 180 to 220 g)were randomly divided into 3 groups(n=10):control group,β_(1)AAbs group and bisoprolol group.Active immunisation ventricular arrhythmia susceptibility model was established by multi-point injection ofβ_(1)-adrenergic receptor second extracellular loop antigenic peptide via the back at 0,2,4 and 6 weeks.Serumβ_(1)AAbs levels at different time points were measured to validate the model.The electrophysiological parameters ventricular effective refractory period,effective refractory period dispersion,conduction velocity and conduction heterogeneity were measured in different regions of the ventricle.Masson staining was used to detect fibrosis levels in different regions of ventricular tissue.Results The level ofβ_(1)AAbs increased significantly from week 2 to week 8 in theβ_(1)AAbs group and the bisoprolol group compared with the control group(P<0.05).Compared with the control and bisoprolol groups,theβ_(1)AAbs group showed a significant increase in heart rate and a significant shortening of RR,QT and QTc intervals(P<0.05);a significant decrease in ventricular effective refractory period in different regions,a significant increase in effective refractory period dispersion(P<0.05),a decrease in conduction velocity in different regions and an increase in conduction heterogeneity(P<0.05),and a significant increase in the percentage of collagen volume in different sites(P<0.05),and the above parameter changes were most pronounced in the middle section,all of which could be reversed by bisoprolol(P<0.05).Conclusionβ_(1)AAbs can increase the electrophysiological properties of ventricular space changes,the underlying mechanism may be related to the degree of fibrosis in dif

关 键 词：β_(1)肾上腺素受体自身抗体 室性心律失常 空间电生理特性 纤维化 比索洛尔 

分 类 号：R541.7[医药卫生—心血管疾病]