[1]薛晓艳,王苗苗,王晓露,等.钠-钙交换体单克隆抗体NCX-2D2对异丙肾上腺素诱发成年大鼠心律失常的抑制作用[J].中国药理学通报,2018,(09):1308-1314.[doi:10.3969/j.issn.1001-1978.2018.09.023]
 XUE Xiao-yan,WANG Miao-miao,WANG Xiao-lu,et al.Inhibitory effect of monoclonal antibody NCX-2D2 on isoproterenol-induced arrhythmias in adult rat hearts[J].Chinese Pharmacological Bulletin,2018,(09):1308-1314.[doi:10.3969/j.issn.1001-1978.2018.09.023]
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钠-钙交换体单克隆抗体NCX-2D2对异丙肾上腺素诱发成年大鼠心律失常的抑制作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年09期
页码:
1308-1314
栏目:
论著
出版日期:
2018-09-26

文章信息/Info

Title:
Inhibitory effect of monoclonal antibody NCX-2D2 on isoproterenol-induced arrhythmias in adult rat hearts
文章编号:
1001-1978(2018)09-1308-07
作者:
薛晓艳1王苗苗1王晓露2杨明珠3吴博威1封启龙1
1.山西医科大学生理学系,细胞生理学省部共建教育部重点实验室,山西 太原 030001; 2.山西医科大学晋祠学院机能教研室,山西 太原 030025; 3.中山大学中山医学院,广东 广州 510080
Author(s):
XUE Xiao-yan1 WANG Miao-miao1 WANG Xiao-lu2 YANG Ming-zhu3 WU Bo-wei1 FENG Qi-long1
1.Dept of Physiology, Shanxi Medical University, Key Lab of Cellular Physiology of Shanxi Province and Ministry of Education, Taiyuan 030001, China; 2.Dept of Functioning, Jinci College of Shanxi Medical University, Taiyuan 030025, China; 3.Dept of Medicine, Sun Yat-sen University, Guangzhou 510080, China
关键词:
钠-钙交换体 L-型钙通道 心律失常 单克隆抗体 全细胞膜片钳技术 延迟后除极
Keywords:
Na+-Ca2+ exchanger L-type calcium channel cardiac arrhythmia monoclonal antibody whole-cell patch clamp delayed afterdepolarization
分类号:
R-332; R322.11; R348.1; R392.11; R541.702.2
DOI:
10.3969/j.issn.1001-1978.2018.09.023
文献标志码:
A
摘要:
目的 观察钠-钙交换体单克隆抗体NCX-2D2对异丙肾上腺素(isoproterenol,ISO)诱发大鼠心律失常的影响,并探讨其电生理机制。 方法 利用ISO建立大鼠离体和在体心律失常模型,观察NCX-2D2抗体对心律失常的影响; 通过全细胞膜片钳技术,观察NCX-2D2抗体对大鼠心室肌细胞INa/Ca、ICa-L和DADs的作用。结果 10 mg·L-1 2D2抗体可明显抑制ISO诱发大鼠离体心脏心律失常的发生(P<0.01); 80 μg·kg-1 2D2抗体可明显抑制ISO诱发麻醉大鼠心律失常的发生(P<0.01); 5 mg·L-1 2D2抗体可部分抑制ISO对大鼠心室肌细胞INa/Ca的增大作用(P<0.01),以及对ICa-L的增大效应(P<0.01),并可有效抑制ISO诱发大鼠心室肌细胞DADs的发生(P<0.05)。结论 钠-钙交换体单克隆抗体NCX-2D2可明显抑制异丙肾上腺素诱发的大鼠室性心律失常,其抗心律失常机制与抑制心肌细胞钠-钙交换体和L-型钙通道,从而减轻钙超载和抑制延迟后除极有关。
Abstract:
Aim To investigate the effects of monoclonal antibody NCX-2D2 on isoproterenol -induced arrhythmias in rat hearts, and to explore the electrophysiological mechanism. Methods Using isoproterenol to establish in vitro and in vivo arrhythmic rat models to observe the effect of NCX-2D2 antibody on ventricular arrhythmias in rats. The whole-cell patch clamp technique was used to investigate the effects of NCX-2D2 antibody on INa/Ca, ICa-L at voltage-clamp mode and on DADs at current-clamp mode in single rat ventricular myocytes. Results 10 mg·L-1 NCX-2D2 antibody significantly inhibited cardiac arrhythmias induced by ISO in vitro(P<0.01). 80 μg·kg-1 NCX-2D2 antibody markedly inhibit the occurrence of arrhythmias in ISO-induced anesthetized rats in vivo(P<0.01). 5 mg·L-1 NCX-2D2 antibody partially inhibited the increase of INa/Ca(P<0.01)and the increase of ICa-L(P<0.01), and could effectively inhibit ISO-induced DADs in rat ventricular myocytes(P<0.05). Conclusions The sodium-calcium exchanger monoclonal antibody NCX-2D2 significantly inhibits isoproterenol-induced ventricular arrhythmias in rats. The mechanism against ventricular arrhythmias is mainly due to its inhibition of cardiomyocyte sodium-calcium exchanger and L-type calcium channel and marked suppression of DADs in rat ventricular myocytes.

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备注/Memo

备注/Memo:
收稿日期:2018-05-10,修回日期:2018-06-22
基金项目:山西省归国留学人员基金资助项目(No 2017-055); 山西省重点实验室建设项目(No 2015012003-08); 山西省高等学校优秀青年学术带头人支持项目; 山西省“1331工程”重点学科建设计划经费资助
作者简介:薛晓艳(1990-),女,硕士生,研究方向:心肌电生理,E-mail:773769165@qq.com;
封启龙(1976-),男,博士,教授,硕士生导师,研究方向:心肌电生理,通讯作者,E-mail: fengqilong@163.com
更新日期/Last Update: 2018-08-26