静脉输注瑞芬太尼诱发大鼠心肌氧化应激水平的效应

Effects of intravenous remifentanil infusion on myocardial oxidative stress in rats

目的评价静脉输注瑞芬太尼诱发大鼠心肌氧化应激水平的效应。方法健康雄性SD大鼠180只，体重250—300g，5—6月龄，采用随机数字表法，将其随机分为15组（n=12）：对照组（c组）、缺血预处理组（IPC组）、瑞芬太尼预处理组（RPC组）及静脉输注瑞芬太尼组，静脉输注瑞芬太尼组速率分别为1、5、10、20μg·kg^-1·min^-1，输注时间分为15、60、120min，分别为R1-15组、R1-60组、R1-120组、R5-15组、R5-60组、R5-120组、R10-15组、R10-60组、R10-120组、R20-15组、R20-60组和R20-120组。在动脉圆锥与左心耳之间左冠状动脉前降支下穿线，15min后进行分组处理。采用结扎左冠状动脉前降支进行心肌缺血，IPC组心肌缺血5min，再灌注5min，共3个循环；RPC组静脉输注瑞芬太尼5ug·kg^-1·min^-1 5min，暂停5min，共3个循环。每组取6只大鼠，于分组处理30main时进行心肌缺血30min，再灌注120min时取心肌组织，测定心肌梗死面积。每组取另外6只大鼠，于分组处理结束后取心肌组织，测定氧自由基、丙二醛和硝基酪氨酸的水平。结果与c组比较，IPC组、RPC组、R1-120组、R5-60组、R5-120组和R10-60组心肌梗死面积缩小，R1-120组、R5-60组、R5-120组、R10-60组、R10-120组、R20-15组、R20-60组和R20-120组心肌组织氧自由基表达上调，R20-15组、R20-60组和R20-120组心肌组织丙二醛和硝基酪氨酸的含量升高（P〈0．05或0．01）。结论高速率和长时间输注瑞芬太尼可诱发大鼠心肌氧化应激反应。

Objective To investigate the effects of intravenous （iv） remifentanil infusion on myocardial oxidative stress in rats. Methods One hundred and eighty male SD rats weighing 250-300 g were randomly divided into 15 groups （n = 12 each）： group control （group C）; group ischemic preconditioning （group IPC）; group remifentanil preconditioning （group RPC） ; while in iv remifentanil infusion groups, iv remifentauil was infused at 4 different rates （ 1, 5, 10, 20 ug·kg^-1·min^-1） and each rate was maintained for 15, 60 and 120 min respectively. Myocardial ischemia was induced by occlusion of left coronary artery anterior descending branch for 30 min followed by 120 min reperfusion in 6 rats in each group. In group IPC myocardial isehemia was preceded by 3 cycles of 5 min ischemia-5 min reperfusion; while in group RPC 3 cycles of 5 min remifentanil infusion at 5ug·kg^-1·min^-1 were applied at 5 min interval before ischemia. Six rats in which UR was produced were sacririced in each group, myocardial infarct size （IS） and the area at risk （AAR） were measured and IS/AAR was calculated. The left 6 rats in each group were sacrificed at the corresponding time point （the end of each treatment） and superoxide radical expression and MDA and nitrotyrosine contents in myocardium were determined. Results IS/AAR was significantly decreased in groups IPC, RPC, 1 ug·kg^-1·min^-1× 120 min, 5 ug·kg^-1·min^-1 × 60 or 120 min and 10ug·kg^-1·min^-1 x 60 min as compared with group C. Compared with group C, the myocardial superoxide radical expression was significantly up-regulated in groups 1 ug·kg^-1·min^-1× 120 min, 5ug·kg^-1·min^-1×60 or 120 rain, 10ug·kg^-1·min^-1 ×60 or 120 min and 20ug·kg^-1·min^-1 15, 60 or 120 min, and myocardial MDA and nitrotyrosine contents were significantly increased in group 20ug·kg^-1·min^-1 × 15, 60 or 120 min. Conclusion Longer duration of high rate remifentanil infusion can induce myocardial oxidative stress in rats.