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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2009年第3期

页码:

317-320，328

栏目:

基础研究

出版日期:

2009-05-15

文章信息/Info

Title:

Changes of κ-opioid receptor in myocardium of rats with ischemia and reperfusion and its relationship with I/R

作者:

殷召¹; 李红梅²; 郭海涛¹; 张淑苗¹; 肖安¹; 张权宇¹; 王跃民¹; 裴建明¹

1.第四军医大学基础部生理学教研室，陕西 西安 710032； 2.解放军323医院心内科，陕西 西安 710054)

Author(s):

YIN Zhao¹;  LI Hong-mei²;  GUO Hai-tao¹;  ZHANG Shu-miao¹;  XIAO An¹;  ZHANG Quan-yu¹;  WANG Yue-min¹;  PEI Jian-ming¹

1.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 2.Department of Cardiology, PLA 323rd Hospital, Xi’an 710054, Shaanxi, China

关键词:

缺血/再灌注; κ阿片受体; 心律失常; U50; 488H; nor-BNI

Keywords:

ischemia/reperfusion;  к-opioid receptor;  arrhythmia;  U50; 488H;  nor-BNI

分类号:

R331.3;R364.1

DOI:

-

文献标识码:

A

摘要:

目的 观察κ阿片受体(κ opioid receptor,κ-OR)在抗大鼠心肌缺血/再灌注(ischemia and reperfusion,I/R)中的变化及其与抗I/R性心律失常的关系。方法 将48只SD大鼠随机分为6组，每组8只，即对照组、U50,488H组、I/R组、U50,488H+I/R组、BNI+U50,488H+I/R组和BNI+I/R组，用于建立在体的大鼠I/R模型，观察κ-OR激动剂U50,488H对大鼠心肌I/R模型室性心律失常的影响。另取18只SD大鼠随机分为6组，每组3只，即对照组、假手术组、再灌注即刻组、60、180和360 min组，用于RT-PCR及Western blot检测I/R处理后心肌组织中κ-OR mRNA转录及其蛋白的表达。结果 对照组偶发早搏，I/R组心律失常的发生率明显增加(P<0.01)。给予U50,488H可以明显降低I/R引起的室速和室颤的发生率(P<0.01)及心律失常的评分(P<0.05)。U50,488H抗心律失常的作用可被选择性的κ-OR拮抗剂nor-BNI完全阻断(P<0.01)，而nor-BNI本身对I/R所致心律失常没有影响。RT-PCR的结果发现，κ-OR mRNA的转录水平在再灌注的即刻、再灌注后60及180 min时，明显高于对照组(P<0.01)，在60 min时达到高峰，360 min时恢复到正常水平。Western blot检测表明，在再灌注的即刻、再灌注后60，180 和360 min时，κ-OR蛋白的表达量均明显高于对照组(P<0.05)。结论 在心肌I/R时，κ-OR基因的转录和其蛋白表达的水平明显上调，可能与其抗I/R性心律失常的作用相关。

Abstract:

AIM To investigate the anti-arrhythmic effect of к-opioid receptor (κ-OR) and its changes during myocardial ischemia and reperfusion (I/R). METHODS Forty-eight Sprague- Dawley rats were randomly divided into 6 groups with 8 rats in each group: ①Control group, ②Control+U50,488H group, ③I/R group, ④U50,488H+I/R group, ⑤U50,488H+nor-BNI+I/R group, and ⑥nor-BNI+I/R group. This protocol was used to set up the animal model of myocardial I/R and investigate the effect on ventricular arrhythmic of κ-OR agonist, U50,488H, during I/R. Other Eighteen Sprague-Dawley rats were randomly divided into 6 groups with 3 rats in each group: ①Control group, ②Sham operation group, ③I/R 0 min group, ④I/R 60 min group, ⑤I/R 180 min group, and ⑥I/R 360 min group. This protocol was used to investigate the levels of к-OR mRNA and its protein in rats heart at different time points during I/R by RT-PCR and Western blot, respectively. RESULTS Few ventricular premature contractions were observed in control group and the incidence of arrhythmia in I/R group significantly increased (P<0.01). With pretreatment of U50,488H, the incidence of ventricular tachycardia and ventricular fibrillation (P<0.01) was reduced as well as arrhythmia score in I/R group (P<0.05). With pretreatment of selective κ-OR antagonist (nor-BNI), the anti-arrhythmic effect of U50,488H was completely blocked (P<0.01). But it had no effect on the arrhythmia induced by I/R(P>0.05). Compared with those in control group, the levels of κ-OR mRNA was significantly increased at 0 min, 60 min and 180 min during reperfusion (P<0.01) and increased to utmost amount at 60 min, but decreased to the normal level at 360 min; compared with those in control group, the density of κ-OR protein increased significantly at 0min, 60min, 180min and 360min during reperfusion (P<0.05). CONCLUSION During myocardial I/R, the transcription of κ-OR mRNA and the expression of its protein are increased, which may be related to the anti-arrhythmia effect during myocardial I/R.

参考文献/References

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备注/Memo

备注/Memo:

收稿日期：2007-10-21.基金项目：国家自然科学基金面上项目资助（30770802及30370580）及全军医药卫生科研基金军队“十一五”计划面上项目资助（06MA203） 通讯作者：裴建明，教授，主要从事心脏内分泌的研究Email:Jmpei8@fmmu.edu.cn 作者简介：殷召，本科生Email:yinzhaofmmu@163.com

常用功能

更新日期/Last Update: 2009-05-18