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阿片受体激动剂U50,488H通过Cx43介导的抗心律失常作用与抑制钙通道有关 被引量:5

Anti-arrhythmic effect mediated by regulation of κ-opioid receptor agonist U50,488H on Cx43 is associated with inhibition of calcium channel
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摘要 目的研究U50,488H(选择性κ阿片受体激动剂)是否通过抑制钙通道减少外钙内流参与了κ阿片受体的抗缺血性心律失常作用。方法将30只SD大鼠完全随机设计分为5组(每组6只):对照组(Sham)、缺血组(Isc)、缺血+U50,488H组(Isc+U50)、缺血+U50,488H+钙离子通道激动剂Bay k8644组(Isc+U50+Bay)、缺血+Bay k8644组(Isc+Bay)。建立大鼠急性心肌缺血模型,施行30 min心肌缺血前应用U50,488H(1.5 mg.kg-1)及Bay k8644(66.7μg.kg-1)进行干预,观察各组心律失常发生情况及连接蛋白43(Cx43)在蛋白和基因水平表达的变化。结果①在体动物模型中,Bay k8644可以翻转U50,488H激活κ阿片受体后产生的抗心律失常作用(P<0.05)。②在蛋白表达水平,Bay k8644可以阻断U50,488H对缺血心肌Cx43的保护性上调作用(P<0.01)。③在mRNA表达水平,Bay k8644亦可翻转U50,488H激活κ阿片受体后对缺血心肌Cx43mRNA的调控作用(P<0.01)。结论 U50,488H可通过抑制钙通道减少外钙内流,参与κ阿片受体对缺血心肌Cx43的稳定性调控及抗缺血性心律失常作用。 Aim To investigate whether U50,488H(a selective κ-opioid receptor agonist) participates in the anti-arrhythmic effect mediated by κ-opioid receptor through inhibition of calcium channel and reduction of calcium influx.Methods 30 SD rats were randomly divided into 5 groups(6 rats in each group): control group(Con),ischemia group(Isc),ischemia+U50,488H group(Isc+U50),ischemia+U50,488H+Bay k8644(a calcium channel activator) group(Isc+U50+Bay),ischemia+Bay k8644 group(Isc+Bay).Models of acute myocardial ischemia were established by ligation of the left anterior descending coronary artery in the rats.U50,488H(1.5 mg·kg-1) and Bay k8644(66.7 μg·kg-1) were administered before the 30 min ischemia.Incidence of arrhythmia,changes of Connexin 43(Cx43) protein and mRNA expression in different groups were observed respectively.Results ① In rat models of acute myocardial ischemia,Bay k8644 reversed the anti-arrhythmic effect mediated by κ-opioid receptor stimulation with U50,488H(P0.05).② At the level of protein expression,Bay k8644 blocked the protective up-regulation of Cx43 conferred by U50,488H when ischemia occurred(P0.01).③ At the level of gene expression,Bay k8644 also reversed the stabilization of Cx43 mRNA mediated by κ-opioid receptor stimulation with U50,488H during ischemia(P0.01).Conclusion Through inhibition of calcium channel and reduction of calcium influx,U50,488H participates in the stabilization of Cx43 and anti-arrhythmic effect mediated by κ-opioid receptor when acute myocardial ischemia occurs.
出处 《中国药理学通报》 CAS CSCD 北大核心 2011年第8期1059-1063,共5页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No30971060) 国家新药研究基金项目(No2009ZX09301-009-BD11) 陕西省自然科学基金资助项目(NoS2011JC5080 S2010SF883)
关键词 U50 488H Κ阿片受体 心肌缺血 心律失常 连接蛋白43 钙通道 U50 488H κ-opioid receptor myocardial ischemia arrhythmia Connexin 43 calcium channel
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