中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (11): 1905-1910.doi: 10.4103/1673-5374.219054

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

神经调节蛋白1在心肌梗死后自主神经系统重塑中的作用

  

  • 收稿日期:2017-06-27 出版日期:2017-11-15 发布日期:2017-11-15
  • 基金资助:

    国家重点基础研究发展计划（973计划）（2012CB518604）；国家自然科学基金（81260052）； 湖北省自然科学基金（2014CKB497, 2014BKB075, 和 2015BKA339）；河南省自然科学基金（201602262)

Effects of neuregulin-1 on autonomic nervous system remodeling post-myocardial infarction in a rat model

Xin Lai1, 2, 3, Liang Zhong4, Hai-xia Fu5, Song Dang1, 2, 3, Xin Wang1, 2, 3, Ning Zhang1, 2, 3, Gao-ke Feng1, 2, 3, Zi-qiang Liu1, 2, 3, Xi Wang1, 2, 3, Long Wang2, 3   

  1. 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
    2 Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei Province, China
    3 Hubei Key Laboratory of Cardiology, Wuhan, Hubei Province, China
    4 Wuhan Medical & Healthcare Center for Women and Children, Wuhan, Hubei Province, China
    5 Department of Cardiology, Henan Province People’s Hospital, Zhengzhou, Henan Province, China
  • Received:2017-06-27 Online:2017-11-15 Published:2017-11-15
  • Contact: Xi Wang, M.D., Ph.D. or Long Wang, M.D., Ph.D.,xiwangwhu@163.com or wanglongwhu@163.com.
  • Supported by:

    This work was supported by a grant from the National Key Basic Research Development Program, the “973” Program, No.2012CB518604; the National Natural Science Foundation of China, No. 81260052; the Natural Science Foundation of Hubei Province, No.2014CKB497, 2014BKB075, and 2015BKA339; and the Natural Science Foundation of Henan Province of China, No. 201602262.

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摘要：

交感和迷走神经重塑在心肌梗死后心肌功能的调节中起着重要的作用。最近有研究表明神经调节蛋白1(NRG-1)可以改善心衰后心功能,但是其对心肌梗死后心功能和自主神经重塑的作用少见报道。NRG-1在心肌梗死后自主神经系统重塑中究竟扮演何种角色？实验将45只SD大鼠随机分成3组，假手术组只暴露左前降支冠状动脉,不予结扎，心肌梗死组只结扎左前降支冠状动脉，心肌梗死+ NRG-1组，结扎左前降支冠状动脉后，腹腔内注射0.01ug/kg NRG-1，1次/d，持续7d。 大鼠心肌梗死后4周，采用超声心动图评价心功能，主要测量和计算指标有左心室收缩期内径，左室舒张末期直径，左心室收缩末期容积，左心室舒张末期容积，左心室射血分数和左心室短轴缩短率，并以实时定量PCR 和Western Blot法分别检测缺血心肌组织中酪氨酸羟化酶，生长相关蛋白-43（神经特异蛋白），神经生长因子，胆碱乙酰转移酶（迷走神经标志物）和囊泡乙酰胆碱转运蛋白（心脏迷走神经纤维标志物）的mRNA和蛋白表达水平以反映自主神经重塑情况。结果显示心肌梗死组的心功能较假手术组明显恶化，而注射NRG-1后，心功能得到显著改善；大鼠缺血心肌组织中酪氨酸羟化酶，生长相关蛋白-43，神经生长因子，胆碱乙酰转移酶和囊泡乙酰胆碱转运蛋白mRNA和蛋白表达水平明显升高。而心肌梗死+NRG-1组酪氨酸羟化酶和生长相关蛋白-43 mRNA和蛋白表达水平及胆碱乙酰转移酶mRNA水平较心肌梗死组明显降低，同时神经生长因子和囊泡乙酰胆碱转运蛋白mRNA和蛋白的表达水平及胆碱乙酰转移酶蛋白水平轻微降低。结果表明，NRG-1不仅可以改善心肌梗死后心脏功能，还可以有效调节交感和迷走神经的重塑，实现了自主神经支配的平衡从而保护心肌细胞免受损伤。

orcid:0000-0002-4880-8442(Xi Wang)

关键词: 神经重塑, 心肌梗塞, 神经调节蛋白1, 交感神经, 迷走神经, 动物模型, 实时定量PCR, Western blot 检测法, 心功能

Abstract:

Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction (MI). Increasing evidence indicates that neuregulin-1 (NRG-1) improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups: sham (with the left anterior descending coronary artery exposed but without ligation), MI (left anterior descending coronary artery ligation), and MI plus NRG-1 (left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 (10 μg/kg, once daily for 7 days)). At 4 weeks after MI, echocardiography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 (neuronal specific protein),nerve growth factor, choline acetyltransferase (vagus nerve marker), and vesicular acetylcholine transporter (cardiac vagal nerve fiber marker) in ischem ic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling.
After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG-1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.

Key words: nerve remodeling, myocardial infarction, neuregulin-1, sympathetic nerve, vagus nerve, animal model, real-time PCR, western blot assay, cardiac function, echocardiography