羟考酮后处理对大鼠心肌缺血再灌注损伤的影响

Effect of oxycodone postconditioning on myocardial ischemia-reperfusion injury in rats

目的评价羟考酮后处理对大鼠心肌缺血再灌注损伤的影响。方法清洁级健康成年雄性SD大鼠40只，体重200—300g，采用随机数字表法分为4组（n=10）：假手术组（s组）、心肌缺血再灌注组（I组）、羟考酮后处理组（O组）和PKC选择性抑制剂白屈菜红碱组（CH组）。采用结扎冠状动脉前降支30min、开放120min的方法制备大鼠心肌缺血再灌注损伤模型。s组只穿线，不结扎左冠状动脉前降支；CH组于结扎前经颈静脉缓慢注射白屈菜红碱5mg／kg，给予后立即结扎；O组与CH组于再灌注前2min经颈静脉缓慢注射羟考酮0．5mg／kg。于再灌注120min时颈动脉采集血样，测定血清cTnI和CK—MB的水平。快速处死大鼠后取心脏，采用TTC染色法确定心肌梗死体积。结果与S组比较，I组、O组和CH组血清cTnI和CK—MB水平升高，心肌梗死体积增大（P〈0．05）；与I组比较，O组和CH组血清cTnI和CK—MB水平降低，心肌梗死体积减小（P〈0．05）；与0组比较，CH组血清cTnI和CK-MB水平升高，心肌梗死体积增大（P〈0．05）。结论羟考酮后处理可减轻大鼠心肌缺血再灌注损伤，其机制部分与激活心肌细胞PKC信号通路有关。

Objective To evaluate the effect of oxycodone postconditioning on myocardial ischemia-reperfusion （I/R） injury in rats. Methods Forty pathogen-free heahhy adult male Sprague-Dawley rats, weighing 200-300 g, were randomly divided into 4 groups （n = 10 each） using a random number table： sham operation group （group S）, myocardial I/R group （group I）, oxycodone postconditioning group （group O）, and selective protein kinase C inhibitor chelerythrine group （group CH）. Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery, followed by 120 min reperfusion. In group S, the left anterior descending branch of the coronary artery was only exposed but not ligated. In group CH, chelerythrine 5 mg/kg was injected intravenously and slowly via the jugular vein before ligation which was performed immediately after administration. In O and CH groups, oxycodone 0.5 mg/kg was injected intravenously and slowly via the jugular vein at 2 min before reperfusion. Arterial blood samples were taken at 120 min of reperfusion to detect the levels of cardiac troponin I （eTnI） and ereatine kinase-MB （CK-MB） in serum. The hearts were removed after the animals were sacrificed to measure the myocardial infarct size by TTC staining. Results Compared with group S, the levels of cTnI and CK- MB in serum and myocardial infarct size were significantly increased in I, O and CH groups （P〈O.05）. Compared with group I, the levels of cTnI and CK-MB in serum and myocardial infarct size were significantly decreased in O and CH groups （P〈0.05）. Compared with group O, the levels of cTnl and CK-MB in serum and myocardial infarct size were significantly increased in group CH （P〈0.05）. Conclusion Oxycodone postconditioning can mitigate myocardial I/R injury in rats, and the mechanism is partially related to activation of protein kinase C signaling pathway.