P2X3R对心肌梗死大鼠交感神经重构和室性心律失常的影响  

Effect of P2X3R on Sympathetic Remodeling and Ventricular Arrhythmias in Rats with Myocardial Infarction

作　　者：毕莹莹 杨双 张舒红 唐艳红[1] BI Yingying;YANG Shuang;ZHANG Shuhong;TANG Yanhong(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute of Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院心内科,武汉大学心血管病研究所,心血管病湖北省重点实验室,湖北武汉430060

出　　处：《心血管病学进展》2023年第9期858-864,共7页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(81370282)。

摘　　要：目的 探究嘌呤能配体门控离子通道3受体(P2X3R)信号转导对心肌梗死(MI)后交感神经重构和结构重构以及室性心律失常易感性的影响。方法 成年雄性SD大鼠随机分为3组:(1)sham组;(2)MI组;(3)MI+A317491(MI+A)组。超声心动图评价大鼠心脏功能,酶联免疫吸附测定检测血清和左心室梗死周边区去甲肾上腺素(NE)浓度,记录各组大鼠的心电图分析心率变异性(HRV),记录电生理参数,免疫荧光法染色酪氨酸羟化酶(TH)和生长相关蛋白-43(GAP-43)阳性神经纤维分析自主神经重构,天狼星红染色观察心肌纤维化程度。蛋白质印迹法检测P2X3R、TH、GAP-43、α-平滑肌肌动蛋白、纤维连接蛋白、转化生长因子-β1等蛋白表达水平。结果 与MI组比较,A317491可显著降低MI+A组梗死周边区P2X3R蛋白表达、血清和梗死周边区NE浓度,延长心室有效不应期和动作电位持续时间,改善HRV和室性心律失常诱发率,减轻心肌纤维化,降低心室TH和GAP-43阳性神经密度以及TH和GAP-43蛋白表达,保护心脏功能。结论 A317491可能通过抑制P2X3R改善MI后的交感神经重构和结构重构,保护心脏功能,进一步降低MI后室性心律失常易感性。Objective To explore the effect of purinergic ligand-gated ion channel 3 receptor(P2X3R) signaling on sympathetic remodeling and structural remodeling and the susceptibility to ventricular arrhythmias after myocardial infarction(MI).Methods Male Sprague-Dawley(SD) rats were randomly divided into 3 groups:(1) sham;(2) MI;(3) MI+A317491(MI+A).The heart function was evaluated with echocardiography.The concentrations of norepinephrine(NE) in the serum and the left ventricle were measured by ELISA.Heart rate variability(HRV) and electrophysiological parameters were recorded.Sympathetic remodeling was analyzed by immunofluorescence staining of tyrosine hydroxylase(TH) and growth associated protein-43(GAP-43) positive nerve fibers.The degree of myocardial fibrosis was observed by Sirius red staining.The protein expression levels of P2X3R,TH,GAP-43,α-smooth muscle actin,fibronectin and transforming growth factor-β1 were detected by Western blot.Results Compared with MI group,A317491 significantly reduced the expression of P2X3R in the left ventricle and the NE concentration in the serum and left ventricle.In the terms of electrophysiology,A317491 prolonged the effective refractory period and the action potential duration,improved HRV and ventricular arrhythmias inducibility rate,and decreased myocardial fibrosis,ventricular TH and GAP-43 positive nerve densities and the expression of TH and GAP-43,which also protected the heart function.Conclusion P2X3R antagonist A317491 may promote sympathetic remodeling and structural remodeling with protecting the heart function and further reduce the incidence of ventricular arrhythmias after myocardial infarction.

关 键 词：心肌梗死 室性心律失常 嘌呤能配体门控离子通道3受体 交感神经重构 结构重构 

分 类 号：R542.22[医药卫生—心血管疾病]