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κ-阿片受体激动剂U50488H对内皮素-1所致大鼠室性心律失常的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第3期
页码:
288-292
栏目:
基础研究
出版日期:
2013-06-25

文章信息/Info

Title:
Effect of κopioid receptor agonist U50488H on ventricular arrhythmias induced by ET1 in rats
作者:
冯 娜1; 张志禹2; 王倩梅1; 张淑苗1; 李 娟1; 贾 敏1; 樊 荣1; 王跃民1; 裴建明1
(第四军医大学：1.生理学教研室，2.航空航天医学系五队，陕西 西安 710032)
Author(s):
FENG Na1;  ZHANG Zhiyu2;  WANG Qianmei1;  ZHANG Shumiao1;  LI Juan1;  JIA Min1;  FAN Rong1;  WANG Yuemin1;  PEI Jianming1
(1.Department of Physiology, 2.Faculty of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
κ-阿片受体激动剂; 内皮素-1; 心律失常; 大鼠
Keywords:
U50488H;  endothelin-1;  endothelin-1 receptor;  arrhythmia;  rats
分类号:
R541.7
DOI:
-
文献标识码:
A
摘要:
目的:研究κ-阿片受体选择性激动剂U50488H是否可通过调节内皮素-1(ET-1)表达的水平，进而影响c-Src蛋白酪氨酸激酶(PTK)的表达以实现抗心律失常的作用。方法:将42只大鼠随机分为7组（每组6只）：正常对照组、U50488H组、U50488H+nor-BNI组、nor-BNI组、ET-1组、ET-1+U50488H组及ET-1+U50488H+nor-BNI组。左心室及股动脉插管观测大鼠心率(HR)、动脉压(ABP)、左心室内压(LVP)及心脏收缩和舒张功能(±LVdp/dtmax)等血流动力学指标，并计算大鼠室性心律失常的发生情况和大鼠的死亡率。实时荧光定量PCR检测ET-1及ET-1受体（ETRA）mRNA表达；Western blot测定ETRA及下游分子c-Src PTK的表达水平。结果:U50488H可显著抑制ET-1所致大鼠ABP、LVP以及心脏收缩、舒张功能的升高，并可显著降低ET-1所致大鼠室性心律失常的发生率和死亡率(P<0.01)，以及抑制心肌ET-1 mRNA的水平(P<0.01)。给予ET-1后，磷酸化(P)-c-Src PTK的表达水平升高，U50488H可显著降低c-Src-PTK的水平以及ET-1引起的P-c-Src PTK表达的水平(P<0.05)，此作用可被κ-阿片受体阻断剂nor-BNI所阻断。结论:κ-阿片受体选择性激动剂U50488H可抑制ET-1所致大鼠室性心律失常发生。该作用可能与抑制ET-1及其下游分子c-Src PTK的表达有关。
Abstract:
AIM: To investigate the effect of κ-opioid receptor agonist U50488H on arrhythmia induced by endothelin-1 (ET-1) and the underlying mechanism. METHODS: Rats were randomly divided into 7 groups (6 rats in each group): control group, U50488H group, U50488H+nor-BNI (a selective κ-opioid receptor antagonist) group, norBNI group, ET-1 group, ET-1+U50488H group and ET-1+U50488H+norBNI group. Heart rate (HR), arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+LVdp/dtmax) and diastolic function (LVdp/dtmax) were examined, the arrhythmia score and mortality were determined and the expression of ET-1, ET-1 recepter (ETRA), and cSrc protein tyrosine kinase were assessed. RESULTS: U50488H significantly attenuated the increase in ABP, LVP and ±LVdp/dtmax, and reduced the incidence of ventricular arrhythmias and animal mortality induced by ET-1(P<0.01). U50488H also downregulated myocardial ET-1 mRNA(P<0.01) and cSrc protein tyrosine kinase expressions(P<0.05). In addition, ET-1 stimulated phosphorylation of c-Src protein tyrosine kinase, which was reversed by U50488H(P<0.05). The effect of U50488H was abolished by norBNI, a selective κ-opioid receptor antagonist. CONCLUSION: κ-opioid receptor agonist U50488H reduces ET-1 induced arrhythmia and the effects may be related to the inhibition of the expression of ET-1 and its downstream molecule c-Src protein tyrosine kinase.

参考文献/References

[1]Spinella F,Rosanò L,Di Castro V,et al.Endothelin 1 decreases gap junctional intercellular communication by inducing phosphorylation of connexin 43 in human ovarian carcinoma cells[J].J Biol Chem,2003,278(42):41294-41301.
[2]Sovari AA,Iravanian S,Dolmatova E,et al.Inhibition of cSrc tyrosine kinase prevents angiotensin IImediated connexin 43 remodeling and sudden cardiac death[J].J Am Coll Cardiol,2011,58(22):2332-2339.
[3]张 鹏,朱运龙,王跃民,等.κ-阿片受体激动剂U50488H对大鼠心肌缺血再灌注室性心律失常的影响及作用机制[J].中国临床药理学与治疗学,2006,11(3):251-255.
[4]漆 伟,魏宝珍,王跃民,等.U50488H对大鼠离体心脏的抗心律失常作用[J].第四军医大学学报, 2006,27(9):784-787.
[5]Fryer RM,Hsu AK,Nagase H,et al.Opioidinduced cardioprotection against myocardial infarction and arrhythmias:mitochondrial versus sarcolemmal ATP Sensitive potassium channels[J].J Pharmacol Exp Ther,2000,294(2):451-457.
[6]孙 新,苏 慧,臧益民,等. U50488H对低氧性肺动脉高压大鼠体内一氧化氮、内皮素及血管紧张素Ⅱ水平的影响[J].心脏杂志, 2007, 19(3):249-251,257.
[7]Zhang QY,Wang W,Shi QX,et al.Anti arrhythmic effect mediated by κopioid receptor is associated with the stabilization of Cx43[J].Critical Care Medicine,2010,38(12):2365-2376.
[8]Shi QX,Zhang LJ,Yao Y,et al.κ-opioid receptor activation prevents against arrhythmias by preserving Cx43 protein via alleviation of intracellular calcium[J].Am J Ther,2012,[Epub ahead of print].
[9]田 菲,黄秋菊,王 微,等.κ-阿片受体对心肌Cx43基因及其蛋白表达的调节作用[J].心脏杂志,2011,23(1):35-38.
[10]王 微,吴晓东,时全星,等.阿片受体激动剂U50488H通过Cx43介导的抗心律失常作用与抑制钙通道有关[J].中国药理学通报,2011,27(8):1059-1064.

备注/Memo

备注/Memo:
收稿日期：2012-12-27.
基金项目：国家自然科学基金项目资助(30971060，81270402)
通讯作者：裴建明，教授，主要从事κ阿片受体介导心脏保护研究Email:jmpei8@fmmu.edu.cn
作者简介：冯娜，硕士生Email: cxnna@163.com
更新日期/Last Update: 2013-07-16