CAJ | 학술논문

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.② Cx43 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.③ Cx43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.
목적 관찰κ아편수체선택성격동제(U50488H)급β신상선소수체격동제(이병신상선소,ISO)대대서심장결혈/재관주(ischemia and reperfusion,I/R)인기적심률실상적영향,초보탐토U50488H대심기세포봉극련접단백Cx43적조절궤제.방법 실험대서수궤분위5조즉대조조、I/R조、ISO+I/R조、U50488H+ISO+I/R조、Nor-BNI(κ아편수체조단제)+U50488H+ISO+I/R조.관찰매조심률실상적발생정황병계산심률실상평분,RT-PCR검측Cx43 mRNA표체급용면역조화방법현시대서심기Cx43적분포특정,반정량통계분석.결과 ①심률실상평분:ISO+I/R조고우I/R조(P<0.05),재ISO전급여U50488H칙가이강저ISO인기적심률실상(P<0.05),기효응가피Nor-BNI조단.② Cx43 mRNA수평:ISO+I/R조비I/R조략증고,재ISO전급여U50488H칙가사기인표체수평강저(P<0.05),기효응가피Nor-BNI조단.③ Cx43단백표체:ISO+I/R조Total-Cx43고우I/R조(P<0.05),P-Cx43강저단여I/R조비교차이무통계학의의,급여U50488H후,가제고총Cx43화P-Cx43표체량(P<0.05),기효응가피Nor-BNI조단.결론 κ아편수체격동제가통과억제β신상선소수체대Cx43조절종이발휘항결혈/재관주성심률실상적작용.
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 Cx43mRNA 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.