布托啡诺预先给药对肢体缺血再灌注致大鼠心肌损伤的影响  

Effects of butorphanol pretreatment on myocardial damage induced by limb ischemia/reperfusion in rats

作　　者：王文伟[1] 叶克平[1] 符新春 王华庆[1] 郁丽娜[2] 裘卫东[2] 

机构地区：[1]浙江省台州市第一人民医院麻醉科,318020 [2]浙江大学附属第二医院麻醉科

出　　处：《中华麻醉学杂志》2013年第11期1318-1321,共4页Chinese Journal of Anesthesiology

基　　金：浙江省医学会临床科研基金（2011ZYCA114）

摘　　要：目的评价布托啡诺预先给药对肢体缺血再灌注致大鼠心肌损伤的影响。方法健康雄性sD大鼠108只，体重180～220g，采用随机数字表法，将其分为3组（n=36）：假手术组（S组）、缺血再灌注组（I／R组）和布托啡诺预先给药组（B组）。I／R组和B组采用夹闭双侧股动脉2h恢复灌注的方法制备后肢缺血再灌注诱发大鼠心肌损伤模型。B组缺血前10min右颈内静脉注射布托啡诺注射液0．2mg／kg，I／R组右颈内静脉注射等量生理盐水。各组于缺血前即刻（T0）、再灌注2h（T1）、6h（T2）、12h（T3）、24h（T4）和48h（E）时随机取6只大鼠取腹主动脉血样，采用ELISA法测定血清肌酸激酶同工酶（CK．MB）活性、心肌肌钙蛋白I（cTnI）浓度；随后处死大鼠，取心肌组织，采用TUNEL法检测心肌凋亡细胞，计算心肌细胞凋亡指数；采用Westernblot法测定心肌细胞c-Jun氨基末端激酶（JNK）和细胞外调节蛋白激酶（ERK）的表达水平。结果与s组比较，I／R组T1-5 时血清CK—MB和cTnI水平升高，T2-5时心肌细胞凋亡指数、心肌组织ERK和JNK的表达水平升高（P〈0．05）；与I／R组比较，B组T4时心肌病理学损伤减轻，T2-5时血清CK-MB和cTnI水平降低，T4-5时心肌细胞凋亡指数降低，L2-5时心肌组织ERK的表达水平升高，T2-4时JNK的表达水平降低（P〈0．05）。结论布托啡诺预先给药通过激活MAPK信号传导通路，上调ERK和下调JNK表达，减少心肌细胞凋亡，从而减轻肢体缺血再灌注致大鼠的心肌损伤。Objective To evaluate the effects of butorphanol pretreatment on myocardial damage induced by limb ischemia/reperfusion （I/R） in rats. Methods One hundred and eight male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into 3 groups （ n = 36 each） using a random number table： sham operation group （group S）, I/R group and butorphanol pretreatment group （group B）. Limb ischemia was induced by occlu- sion of bilateral hind limbs for 2 h followed by reperfusion in I/R and B groups. At 10 min before ischemia, butor- phanol 0.2 mg/kg was injected via the right jugular vein in group B, while the equal volume of normal saline was injected in group I/R. Six rats were chosen randomly before ischemia （baseline, T0 ） and at 2, 6, 12, 24 and 48 h after reperfusion （T1-5） and blood samples were taken from the abdominal aorta for determination of the serum creatine kinase isoenzyme-MB （CK-MB） activity and cardiac troponin I （cTnI） concentration. The animals were then sacrificed and myocardial specimens were obtained for determination of myocardial apoptosis （using TUNEL） and the expression of c-Jun N-terminal kinase （JNK） and extracellular signal-regulated protein kinase （ERK） （us- ing Western blot analysis）. Apoptosis index was calculated. Results Compared with group S, the serum CK-MBand cTnI levels were significantly increased at T1-5, and the apoptosis index and expression of JNK and ERK were increased at T2-5 in group I/R （P 〈 0.05）. Compared with group I/R, the pathological changes of myocardium were significantly＇reduced at T4, the serum CK-MB and cTnI levels were decreased at T：_5, the apoptosis index was decreased at T4-5 , the expression of ERK was up-regulated at T1-5, and the expression of JNK was down-regulated at T2-4 （P 〈 0.05）. Conclusion Butorphanol pretreatment can reduce apoptosis in myocardial cells through acti- vating MAPK signal transduction pathway, up-regulating ERK expression and down-regulating JNK expression, thus attenua

关 键 词：布托啡诺 再灌注损伤 四肢 心肌 

分 类 号：R614[医药卫生—麻醉学]