[1]毕莹莹 杨双 张舒红 唐艳红.P2X3R对心肌梗死大鼠交感神经重构和室性心律失常的影响[J].心血管病学进展,2023,(9):858.[doi:10.16806/j.cnki.issn.1004-3934.2023.09.021]
　Bi Yingying,Yang Shuang,Zhang Shuhong,et al.Effect of P2X3R on Sympathetic Remodeling and Ventricular Arrhythmias in Rats with Myocardial Infarction[J].Advances in Cardiovascular Diseases,2023,(9):858.[doi:10.16806/j.cnki.issn.1004-3934.2023.09.021]
点击复制

P2X3R对心肌梗死大鼠交感神经重构和室性心律失常的影响()
分享到：

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2023年9期
页码:
858
栏目:
论著
出版日期:
2023-09-25

文章信息/Info

Title:
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
(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)
Author(s):
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)
关键词:
心肌梗死; 室性心律失常; P2X3R; 交感重构; 结构重构
Keywords:
Myocardial infarction; Ventricular arrhythmias; P2X3R signaling; Sympathetic remodeling; Structural remodeling
DOI:
10.16806/j.cnki.issn.1004-3934.2023.09.021
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功能，ELISA法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。Western blot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可以显著降低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 T H和 GAP-43阳性神经密度以及TH和GAP-43蛋白表达，保护心功能。结论：A317491可能通过抑制P2X3R改善MI后的交感重构和结构重构，保护心功能，进一步降低MI后室性心律失常易感性。
Abstract:
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 nerve 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 ventricular and the NE concentration in the serum and left ventricular. 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

参考文献/References:

[1] Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias[J]. N Engl J Med,1997,337(22):1576-1583.

[2] Ardell JL,Andresen MC,Armour JA,et al. Translational neurocardiology:preclinical models and cardioneural integrative aspects[J]. J Physiol,2016,594(14):3877-3909.

[3] Shivkumar K,Ajijola OA,Anand I,et al. Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics[J]. J Physiol,2016,594(14):3911-3954.

[4] Ford AP. In pursuit of P2X3 antagonists:novel therapeutics for chronic pain and afferent sensitization[J]. Purinergic Signal,2012,8(Suppl 1):3-26.

[5] Li G,Liu S,Zhang J,et al. Increased sympathoexcitatory reflex induced by myocardial ischemic nociceptive signaling via P2X2/3 receptor in rat superior cervical ganglia[J]. Neurochem Int,2010,56(8):984-990.

[6] Pijacka W,Moraes DJ,Ratcliffe LE,et al. Purinergic receptors in the carotid body as a new drug target for controlling hypertension[J]. Nat Med,2016,22(10):1151-1159.

[7] Xue Q,Wang R,Wang L,et al. Downregulating the P2X3 receptor in the carotid body to reduce blood pressure via acoustic gene delivery in canines[J]. Transl Res,2021,227:30-41.

[8] Ye T,Zhang C,Wu G,et al. Pinocembrin decreases ventricular fibrillation susceptibility in a rat model of depression[J]. Front Pharmacol,2020,11:547966.

[9] Ye T,Zhang C,Wu G,et al. Pinocembrin attenuates autonomic dysfunction and atrial fibrillation susceptibility via inhibition of the NF-κB/TNF-α pathway in a rat model of myocardial infarction[J]. Int Immunopharmacol ,2019,77:105926.

[10] 曹克将,陈明龙,江洪,等. 室性心律失常中国专家共识[J]. 中国心脏起搏与心电生理杂志,2016,30(04):283-325.

[11] 杨眉,李毅刚. 心肌梗死后心室颤动的发生机制[J]. 中国心脏起搏与心电生理杂志,2009,23(05):453-455.

[12] Jiang H,Hu X,Lu Z,et al. Effects of sympathetic nerve stimulation on ischemia-induced ventricular arrhythmias by modulating connexin43 in rats[J]. Arch Med Res,2008,39(7):647-654.

[13] Hoffmann BA,Steven D,Willems S,et al. Renal sympathetic denervation as an adjunct to catheter ablation for the treatment of ventricular electrical storm in the setting of acute myocardial infarction[J]. J Cardiovasc Electrophysiol,2013,24(12):E21.

[14] Tao B,Liu Z,Wei F,et al. Over-expression of Kv4.3 gene reverses cardiac remodeling and transient-outward K+ current (Ito) reduction via CaMKII inhibition in myocardial infarction[J]. Biomed Pharmacother ,2020,132:110896.

[15] Ma S,Ma J,Mai X,et al. Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post-myocardial infarction rats[J]. J Cell Mol Med,2019,23(8):5454-5465.

[16] Wang J,Xia Y,Lu A,et al. Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction[J]. Sci Rep,2021,11(1):17722.

[17] Wang HJ,Wang W,Cornish KG,et al. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure[J]. Hypertension,2014,64(4):745-755.

[18] Sheng X,Dan Y,Dai B,et al. Knockdown the P2X3 receptor in the stellate ganglia of rats relieved the diabetic cardiac autonomic neuropathy[J]. Neurochem Int,2018,120:206-212.

[19] Xu X,Liu B,Yang J,et al. Glucokinase in stellate ganglia cooperates with P2X3 receptor to develop cardiac sympathetic neuropathy in type 2 diabetes rats[J]. Brain Res Bull,2020,165:290-297.

[20] Wan F,Li G,Liu S,et al. P2X2/3 receptor activity of rat nodose ganglion neurons contributing to myocardial ischemic nociceptive signaling[J]. Auton Neurosci,2010,158(1-2):58-64.

[21] Wang Y,Li G,Liang S,et al. Role of P2X3 receptor in myocardial ischemia injury and nociceptive sensory transmission[J]. Auton Neurosci,2008,139(1-2):30-37.

[22] Lataro RM,Moraes DJA,Gava FN,et al. P2X3 receptor antagonism attenuates the progression of heart failure[J]. Nat Commun,2023,14(1):1725.

[23] Xu B,Xu H,Cao H,et al. Intermedin improves cardiac function and sympathetic neural remodeling in a rat model of post myocardial infarction heart failure[J]. Mol Med Rep,2017,16(2):1723-1730.

[24] Zhou M,Liu Y,He Y,et al. Selective chemical ablation of transient receptor potential vanilloid 1 expressing neurons in the left stellate ganglion protects against ischemia-induced ventricular arrhythmias in dogs[J]. Biomed Pharmacother,2019,120:109500.

相似文献/References:

[1]王铁华,郑景辉,莫云秋.蛋白质组学在心肌梗死中的研究进展[J].心血管病学进展,2015,(5):616.[doi:10.3969/j.issn.1004-3934.2015.05.024]
　WANG Tiehua,ZHENG Jinghui,MO Yunqiu.Research Progress of Proteomics in Myocardial Infarction[J].Advances in Cardiovascular Diseases,2015,(9):616.[doi:10.3969/j.issn.1004-3934.2015.05.024]
[2]张耀庭 李烽 朱永翔 陆丽洁 龙明智.沙库巴曲/缬沙坦在室性心律失常中的研究进展[J].心血管病学进展,2019,(7):982.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.004]
　ZHANG Yaoting,LI Feng,ZHU Yongxiang,et al.Research Progress of Sacubitril/Valsartan in Ventricular Arrhythmia[J].Advances in Cardiovascular Diseases,2019,(9):982.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.004]
[3]孙洋.基质金属蛋白酶与心肌梗死后心脏重构[J].心血管病学进展,2019,(8):1094.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.006]
　SUN Yang.Matrix Metalloproteinases in Cardiac Remodeling after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2019,(9):1094.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.006]
[4]陈丰 苏强 朱继金.高迁移率族蛋白B1在心脏炎症反应性疾病中的研究进展[J].心血管病学进展,2019,(8):1111.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.010]
　CHEN Feng,SU Qiang,ZHU Jijin.Research Progress of HMGB1 in Myocardial Inflammatory Reactivity Disease[J].Advances in Cardiovascular Diseases,2019,(9):1111.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.010]
[5]常文婧 王丽娜.Hippo通路在心脏发育、再生和疾病中的作用[J].心血管病学进展,2019,(8):1115.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.011]
　CHANG Wenjin,WANG Lina.Role of Hippo Pathway in Heart Development,Regeneration and Disease[J].Advances in Cardiovascular Diseases,2019,(9):1115.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.011]
[6]王宇 周思维 张莎 吴弘.植入型心律转复除颤器在心肌梗死后心脏性猝死中的研究进展[J].心血管病学进展,2020,(1):4.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.002]
　WANG Yu,ZHOU Siwei,ZHANG Sha,et al.Implantable Cardioverter Defibrillator in Sudden Cardiac Death after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2020,(9):4.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.002]
[7]梁砚薷李晶洁.神经元型钠通道在室性心律失常发生机制中的作用[J].心血管病学进展,2020,(1):43.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.012]
　LIANG Yanru,LI Jingjie.Role of Neuronal Sodium Channels in Development of Ventricular Arrhythmias[J].Advances in Cardiovascular Diseases,2020,(9):43.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.012]
[8]刘磊 杨震.心肌梗死后左心室壁瘤相关室性心律失常的形成机制与治疗进展[J].心血管病学进展,2020,(1):46.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.013]
　LIU Lei,YANG Zhen.Mechanism and Progress in Treatment of Post-infarction Left Ventricular Aneurysm with Ventricular Arrhythmias[J].Advances in Cardiovascular Diseases,2020,(9):46.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.013]
[9]邹先明 赵然尊.长链非编码RNA ANRIL与心血管疾病的研究进展[J].心血管病学进展,2020,(2):167.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.017]
　ZOU Xianming,ZHAO Ranzun.Long Non-Coding RNA ANRIL and Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2020,(9):167.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.017]
[10]王茜 李晶洁.细胞学机制在调控心肌梗死后炎症反应中的研究进展[J].心血管病学进展,2020,(2):190.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.023]
　WANG QianLI Jingjie.Cytological Mechanisms in Regulation of The Post-infarction Inflammatory Response[J].Advances in Cardiovascular Diseases,2020,(9):190.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.023]
[11]王思博 王连生.心肌梗死后室性心律失常的治疗进展[J].心血管病学进展,2021,(6):481.[doi:10.16806/j.cnki.issn.1004-3934.2021.06.001]
　WANG SiboWANG Liansheng.Treatment of Ventricular Arrhythmias after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2021,(9):481.[doi:10.16806/j.cnki.issn.1004-3934.2021.06.001]

更新日期/Last Update: 2023-10-17