δ、κ阿片受体对舒芬太尼预处理大鼠心肌缝隙连接蛋白43的影响

The effect of δ and κ opioid receptors on myocardial connexin 43 in sufentanil preconditioning in rats

目的观察δ、κ阿片受体对舒芬太尼预处理大鼠心肌缝隙连接蛋白43（Cx43）的影响,探讨舒芬太尼抗缺血性心律失常的机制。方法健康雄性SD大鼠30只,2~3个月月龄,体重250~330g。采用随机数字表法将大鼠分为五组：对照组（C组）,缺血-再灌注组（IR组）,舒芬太尼预处理组（S组）,δ受体拮抗剂纳曲吲哚＋舒芬太尼预处理组（NS组）,以及κ受体拮抗剂nor-BNI＋舒芬太尼预处理组（BS组）。C组不结扎;IR组采用结扎左冠状动脉30min,再灌注120min的方法建立心肌缺血-再灌注损伤模型;S组在心肌缺血前给予舒芬太尼3μg/kg输注5min,停止5min,重复3次进行预处理;NS组和BS组分别于给舒芬太尼前10min和15min静脉注射纳曲吲哚和nor-BNI 5mg/kg。记录心电图并对缺血30min和再灌注30min进行心律失常评分。于心肌缺血-再灌注末处死大鼠,留取左心室心肌组织,行免疫组化染色法检测Cx43蛋白的表达;行RT-PCR技术检测大鼠心肌组织中Cx43 mRNA的表达。结果IR组、NS组和BS组心律失常评分明显高于C组（P〈0.05）;S组和NS组心律失常评分明显低于IR组（P〈0.05）;BS组心律失常评分明显高于S组（P〈0.05）。IR组、S组、NS组和BS组Cx43表达均明显低于C组（P〈0.05）;S组Cx43表达明显高于IR组（P〈0.05）;NS组和BS组Cx43表达明显低于S组（P〈0.05）。结论δ和κ阿片受体可能参与了舒芬太尼预处理上调心肌Cx43表达的过程,且κ阿片受体在抗缺血性心律失常中起到主导作用。

Objective To investigate the association between the changes of Cx43 in the myocardial protection by sufentanil preconditioning and the opioid receptorsδandκ,explore the mechanism of sufentanil preventing myocardium from ischemia reperfusion injury.Methods Thirty adult male Sprague-Dawley rats,aged 2-3months,weighed 250-330 g,were randomly divided into 5groups（n=6）：control group（C）,ischemia-reperfusion group（IR）,sufentanil preconditioning group（S）,naltrindole＋sufentanil preconditioning group（NS）,nor-binaltorphimine＋sufentanil preconditioning group（BS）.In group S,sufentanil 3μg/kg was administered via a venous pump thrice before ligating the left anterior descending coronary,each administration lasted for 5min with a 5min interval in-between.In group NS and group BS,naltrindole（δopioid receptor antagonist）and nor-binaltorphimine（κopioid receptor antagonist）,5mg/kg,were administered intravenously 10 min and 15 min respectively before sufentanil preconditioning.The electrocardiogram was recorded and scored for arrhythmia.The rats were then sacrificed and the ventricular tissue was adopted for the later determination.An immunohistochemical staining was used to detect the expression of Cx43 protein in myocardial cells and RT-PCR was used to detect the amount of Cx43 mRNA.Results Compared with group C,the arrhythmia scores in groups IR,BS and NS were increased（P〈0.05）;Compared with group IR,the arrhythmia scores in groups S and NS were decreased（P〈0.05）;Compared with group S,the arrhythmia scores in group BS was increased（P〈0.05）.Compared with group C,the expression of Cx43 in the other four groups were decreased（P〈0.05）.Compared with group IR,the expression of Cx43 in group S was increased（P〈0.05）.Compared with group S,the expression of Cx43 in groups NS and BS were decreased（P〈0.05）.Conclusion δandκopioid receptors may participate in the process that sufentanil preconditioning upregulate the expression of Cx43 in myocardium andκopioid receptor plays a dominant role against ischemic arrhythmia.