к阿片受体可通过抑制β肾上腺素受体进而调节心肌细胞Cx43发挥抗缺血/再灌注性心律失常  

Antiarrhythmic effect of κ-opioid on Cx43 in rat heart during mycardial ischemia and reperfusion via inhibiting β-adrenergic receptor pathway

作　　者：王伟光[1] 张权宇[2] 曹钰琨[1] 郑奇军[1] 徐学增[1] 王跃民[2] 俞世强[1] 裴建明[2] 

机构地区：[1]第四军医大学西京医院心脏外科,陕西西安710032 [2]第四军医大学基础部生理学教研室,陕西西安710032

出　　处：《中国药理学通报》2010年第4期471-476,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30770802;30971060)

摘　　要：目的观察κ阿片受体选择性激动剂(U50488H)及β肾上腺素受体激动剂(异丙肾上腺素,ISO)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)引起的心律失常的影响,初步探讨U50488H对心肌细胞缝隙连接蛋白Cx43的调节机制。方法实验大鼠随机分为5组即对照组、I/R组、ISO+I/R组、U50488H+ISO+I/R组、Nor-BNI(κ阿片受体阻断剂)+U50488H+ISO+I/R组。观察每组心律失常的发生情况并计算心律失常评分,RT-PCR检测Cx43 mRNA表达及用免疫组化方法显示大鼠心肌Cx43的分布特征,半定量统计分析。结果①心律失常评分:ISO+I/R组高于I/R组(P<0.05),在ISO前给予U50488H则可以降低ISO引起的心律失常(P<0.05),其效应可被Nor-BNI阻断。②Cx43 mRNA水平:ISO+I/R组比I/R组略增高,在ISO前给予U50488H则可使基因表达水平降低(P<0.05),其效应可被Nor-BNI阻断。③Cx43蛋白表达:ISO+I/R组Total-Cx43高于I/R组(P<0.05),P-Cx43降低但与I/R组比较差异无统计学意义,给予U50488H后,可提高总Cx43和P-Cx43表达量(P<0.05),其效应可被Nor-BNI阻断。结论κ阿片受体激动剂可通过抑制β肾上腺素受体对Cx43调节从而发挥抗缺血/再灌注性心律失常的作用。Aim To investigate the effect of U50488H（a selective κ-opioid receptor agonist）and isoproterenol（ISO,a β-adrenergic receptor agonist）on ventricular arrhythmias and Cx43 during myocardial ischemia and reperfusion in rats.Methods 60 rats were randomly divided into five groups,ie,normal control group,I/R group,ISO＋I/R group,U50488H＋ISO＋I/R group,Nor-BNI＋U50488H＋ISO＋I/R group.The incidence of ventricular arrhythmias and arrhythmia score were determined. The expression of Cx43 mRNA was tested by RT-PCR.The expression of Cx43 protein in myocardial cell was tested by an immunohistochemical approach with a quantitative imaging system.Results ① Compared with the I/R group,arrhythmia score was increased with administration of ISO（P〈0.05）.U50488H intravenously injected before ISO significantly decreased the arrhythmia score（P〈0.05）.② Compared with the normal control group,the expression of Cx43 mRNA was decreased in the I/R group（P〈0.05）.With administration of ISO,the amount of Cx43 mRNA was not significantly increased.③ Compared with normal control group,total and phosphorylated Cx43 proteins were significantly decreased in the I/R group（P〈0.05）,and the phosphorylated Cx43 was also decreased with administration of ISO.Compared with ISO＋I/R group,phosphorylated Cx43 was increased with administration of U50488H （P〈0.05）.Conclusion κ-opioid receptor agonist U50488 H antagonizes the arrhythmias through the regulation of Cx43 during myocardial ischemia and reperfusion via inhibiting β-adrenergic receptor pathway.

关 键 词：U50488H 异丙肾上腺素 缺血/再灌注 心律失常 CX43 Κ阿片受体 

分 类 号：R332[医药卫生—人体生理学] R322.11[医药卫生—基础医学]