桥粒重塑参与β1肾上腺素能受体自身抗体诱导的室性心律失常  

Desmosome remodeling involved in ventricular arrhythmias induced byβ1-adrenergic receptor autoantibodies

作　　者：宋洁 孙华鑫 张小雪 薄雅坤 喜林强 杨娜 曼则热姆·热杰普 张玲[1] 汤宝鹏[1] 周贤惠[1] Song Jie;Sun Huaxin;Zhang Xiaoxue;Bo Yakun;Xi Linqiang;Yang Na;Manzeremu Rejiepu;Zhang Ling;Tang Baopeng;Zhou Xianhui(Department of Cardiac Pacing and Electrophysiology,The First Affiliated Hospital of Xinjiang Medical University,Xinjiang Key Laboratory of Cardiac Electrophysiology and Remodeling,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院心脏起搏电生理科、新疆心电生理与心脏重塑重点实验室,乌鲁木齐830054

出　　处：《中华心律失常学杂志》2023年第1期71-78,共8页Chinese Journal of Cardiac Arrhythmias

基　　金：国家自然科学基金(81660053);新疆维吾尔自治区自然科学基金重点项目(2022D01D15)。

摘　　要：目的在主动免疫兔模型中探讨桥粒重塑在β1肾上腺素能受体自身抗体(β1ARAbs)诱导的室性心律失常(VA)的作用及潜在机制。方法18只新西兰大白兔(体重2.5~3.5 kg)依据随机数字表法分为3组:模型组(β1ARAbs组,6只)、干预组(Meto组,6只)和对照组(Con组,6只)。经背部多点注射β1肾上腺素能受体胞外第二环抗原肽(2 mg/只)建立动物模型。0、2、4、6和8周时测定抗体水平,8周时记录并比较各组左心室射血分数(LVEF)、VA负荷及心室有效不应期(VERP),检测桥粒结构和桥粒重塑相关蛋白水平。结果与Con组和Meto组比,β1ARAbs组VA发生次数增加[(397.67±50.81)次对(32.67±3.76)次对(96.33±8.25)次,P均<0.001],VA持续时间延长[(164.13±10.79)s对(14.95±1.05)s对(57.61±5.27)s,P均<0.001],LVEF水平(55.97%±2.82%对76.44%±2.00%对70.58%±0.55%,与Con组比较,P<0.001;与Meto组比较,P=0.002)和VA诱发率(75%对6%对8%,P均<0.001)升高;VERP缩短[(115.92±2.24)ms对(136.33±5.80)ms对(131.90±4.38)ms,与Con组比较,P=0.005;与Meto组比较,P=0.025]。蛋白免疫印迹结果显示,β1ARAbs组磷酸化细胞外信号调节激酶(p-ERK)水平升高(2.30±0.16对0.18±0.08对1.43±0.20,与Con组比,P<0.001;与Meto组比,P<0.007)。结论β1ARAbs增加VA负荷和持续时间,加重心室重构和VA易感性,潜在机制与ERK信号介导的心肌细胞间桥粒重塑增强有关。Objective To explore the role of desmosome remodeling inβ1-adrenergic receptor autoantibodies(β1ARAbs)induced ventricular arrhythmia(VA)in active immune rabbit model and its potential mechanism.Methods Eighteen New Zealand white rabbits(body weight 2.5-3.5 kg)were randomly divided into 3 groups(6 in each group):β1ARAbs model group(β1ARAbs group),intervention group(Meto group)and control group(Con group).Multi point injection via back extracellular second cyclic peptide antigen peptide(2 mg each)ofβ1-adrenergic receptor to establish animal model.Antibody levels were measured at 0,2nd,4th,6th and 8th week.Heart rate,left ventricular ejection fraction(LVEF),VA burden and ventricular effective refractory period(VERP)were recorded at 8th week.The desmosome structure and desmosome remodeling related protein levels were detected.Results Compared with Con group and Meto group,β1ARAbs increased the frequency of VA[(397.67±50.81)times vs.(32.67±3.76)times vs.(96.33±8.25)times,all P<0.001],prolonged the duration of VA[(164.13±10.79)s vs.(14.95±1.05)s vs.(57.61±5.27)s,all P<0.001],increased LVEF levels(55.97%±2.82%vs.76.44%±2.00%vs.70.58%±0.55%,compared with Con group,P<0.001;compared with Meto group,P=0.002)and VA induction rate(75%vs.6%vs.8%,all P<0.001),shortened VERP[(115.92±2.24)ms vs.(136.33±5.80)ms vs.(131.90±4.38)ms,compared with Con group,P=0.005;compared with Meto group,P=0.025].Western blotting results showed that the level of phosphorylated extracellular signal-regulated kinase(p-ERK)was increased(2.30±0.16 vs.0.18±0.08 vs.1.43±0.20,compared with Con group,P<0.001;compared with Meto group,P=0.007)in theβ1ARAbs group.Conclusionβ1ARAbs increased the burden and duration of VA,aggravated ventricular remodeling and susceptibility to VA.The potential mechanism was related to the potentiation of desmosome remodeling mediated by ERK signaling.

关 键 词：桥粒 室性心律失常 β1肾上腺素能受体自身抗体 缝隙连接 兔 

分 类 号：R541.7[医药卫生—心血管疾病]