摘要
目的 评价细胞外信号调节蛋白激酶1/2（ERK1/2）信号通路在二氮嗪后处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 健康成年雄性SD大鼠60只,体重240 - 260 g,3月龄,采用随机数字表法,将其分为5组（n=12）：假手术组（S组）、缺血再灌注组（I/R组）、溶媒组（V组）、二氮嗪后处理组（D组）和ERK1/2信号通路抑制剂U0126组（U组）.采用阻断左冠状动脉前降支30 min,再灌注120m in的方法制备心肌缺血再灌注损伤模型.V组和D组分别于再灌注即刻经股静脉注射0.4％二甲基亚砜1ml和二氮嗪7 mg/kg,U组于再灌注前10 min经股静脉注射U0126 500μg/kg,其余处理同D组.于再灌注120 min时,取心肌组织检测心肌梗死体积,采用TUNEL法计算细胞凋亡指数,RT-PCR法检测心肌组织ERK1/2 mRNA的表达水平;Western blot法检测心肌组织总ERK1/2（t-ERK1/2）和磷酸化ERK1/2（p-ERK1/2）蛋白的表达水平.结果 与S组比较,其余各组心肌梗死体积和细胞凋亡指数升高,I/R组、V组和U组心肌组织ERK1/2 mRNA和p-ERK1/2蛋白表达下调（P＜0.05）,D组心肌组织ERK1/2 mRNA和p-ERK1/2蛋白表达差异无统计学意义（P＞0.05）;与I/R组比较,D组心肌梗死体积和细胞凋亡指数降低,心肌组织ERK1/2 mRNA和p-ERK1/2蛋白表达上调（P＜0.05）,V组、U组上述指标差异无统计学意义（P＞0.05）;与D组比较,U组心肌梗死体积和细胞凋亡指数升高,心肌组织ERK1/2 mRNA和p-ERK1/2蛋白表达下调（P＜ 0.05）. 5组间心肌组织t-ERK1/2蛋白表达比较差异无统计学意义（P＞0.05）.结论 二氮嗪后处理可能通过激活ERK1/2信号通路减轻大鼠心肌缺血再灌注损伤.
Objective To evaluate the role of ERK1/2 signaling pathway in mitigation of myocardial ischemia-reperfusion （I/R） injury by diazoxide postconditioriing in rats.Methods Sixty adult male SpragueDawley rats,aged 3 months,weighing 240-260 g,were randomly divided into 5 groups （n =12 each） using a random number table：sham operation group （S group）,I/R group,vehicle group （Ⅴ group）,diazoxide postconditioning group （D group）,and ERK1/2 signaling pathway inhibitor U0126 group （U group）.Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion.In V and D groups,0.4％ DMSO and diazoxide 7 mg/kg （in 1 ml 0.4％ DMSO） were administrated,respectively,through the femoral vein at the onset of the reperfusion.In U group,U0126 was given through the femoral vein at 10 min before reperfusion,and the following procedures were similar to those previously described in group D.At 120 min of reperfusion,myocardial specimens were obtained for detection of myocardial infarct size,cell apoptosis （using TUNEL）,and expression of ERK1/2 mRNA （by RT-PCR）,total ERK1/2 （t-ERK1/2） and phosphorylated ERK1/2 （p-ERK1/2） （by Western blot）.Apoptosis index was calculated.Results Compared with S group the myocardial infarct size and apoptosis index were significantly increased in the other groups,the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in I/R,V and U groups,and no significant change was found in the expression of ERK1/2 mRNA and p-ERK1/2 in Dgroup.Compared with I/R group,the myocardial infarct size and apoptosis index we re significantly decrcaed,and the expression of ERK1/2 mRNA and p-ERK1/2 was up-regulated in D group,and no significant change was foundin the parameters mentioned above in V and U groups.Compared with D group,the myocardial infarct sizeand apoptosis index were significantly increased,and the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in U group.There was no significant
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第12期1485-1488,共4页
Chinese Journal of Anesthesiology
关键词
细胞外信号调节MAP激酶类
二氮嗪
缺血后处理
心肌再灌注损伤
Extracellular signal-regulated MAP kinases
Diazoxide
Ischemic postconditioning
Myocardial reperfusion injury
