右美托咪定通过c-jun氨基末端激酶和p38通路减轻大鼠脑缺血再灌注损伤  

Dexmedetomidine attenuates cerebral ischemia-reperfusion injury by inhibiting c-Jun N-terminal kinase and p38 pathway in rats

作　　者：金峰[1] 张舒驰[1] 赵冰晓 艾艳秋[1] 

机构地区：[1]郑州大学第一附属医院麻醉科,450052

出　　处：《中华实验外科杂志》2017年第8期1296-1298,共3页Chinese Journal of Experimental Surgery

摘　　要：目的 观察右美托咪定（Dex）在脑缺血再灌注损伤中对p38和c-jun氨基末端激酶（JNK）的表达和下游凋亡信号半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3的表达的影响,探讨其脑保护效应的机制.方法 健康雄性SD大鼠54只,体重240~280g,采用随机数字表法分为3组（n=18）：假手术组（S组）、脑缺血再灌注组（I/R组）和Dex组.I/R组和Dex组采用线栓法制备大鼠脑缺血再灌注损伤模型,缺血90min后再灌注24h;Dex组缺血同时经尾静脉泵注3μg/kg Dex于5min内泵完,6μg/（kg＆#183;h）持续泵注2 h.S组和I/R组泵注等量生理盐水.于再灌注24h时行神经功能缺陷评分,取脑组织,氯化三苯基四氮唑（TTC）法测定脑梗死体积,计算脑梗死体积百分比;干湿法测定脑含水量;采用免疫荧光法检测脑组织中磷酸化JNK（p-JNK）、磷酸化p38（p-p38）、活化Caspase-3（cleaved Caspase-3）,采用Western blot检测JNK、p38、p-JNK和p-p38表达水平.结果 神经功能缺陷评分[（2.16±0.63）、（2.86±0.45）分,F=136.500,P=0.000]、脑含水量[（79.16±1.50）%、（85.23±1.19）%,F=162.777,P=0.000]和脑梗死体积百分比[（20.09±1.62）%、（28.53±1.68）%,F=707.707,P=0.000] Dex组均小于I/R.与I/R组比较,Dex组p-p38（18.67±2.73、32.33±3.01,F=210.481,P=0.000）、p-JNK（17.83±2.48、35.33±3.20,F=257.534,P=0.000）和cleaved Caspase-3表达阳性细胞数（33.00±3.58、51.50±3.62,F=346.888,P=0.000）均较少.与I/R组比较,Dex组p-p38（2.08±0.19比1.38±0.11,F=190.834,P=0.000）和p-JNK（35.33±3.20比17.83±2.48,F=514.456,P=0.000）均表达减少.结论 Dex定减轻大鼠脑缺血再灌注损伤,其机制与抑制JNK 和p38的磷酸化,从而减少Caspase-3 的激活有关.Objective To establish cerebral ischemia reperfusion injury induced by middle cerebral artery occlusion （MCAO）,and investigate whether the effect of dexmedetomidine （Dex） on the cerebral ischemia reperfusion （I/R） injury is connected with c-Jun N-terminal kinase （JNK） and p38 pathways.Methods Fifty-four adult male SD rats,weighing 240-280 g,were randomly divided into three groups： sham group,I/R group and Dex group.I/R group and Dex group were subjected to cerebral ischemia,which was induced by the MCAO.Dex group was administered with Dex when ischemia began through the tail vein at 3 μg/kg for 5 min,then at the speed of 6 μg/（kg＆#183;h） dose of continuous pumping for 2 h.Sham group and I/R group were given equal volume of normal saline at the same time points.After 90 min ischemia and 24 h reperfusion,animals were evaluated for motor-deficits,then sacrificed for further analysis.The wet minus dry weight method was applied for the analysis of brain water content,staining with 2% triphenyltetrazolium chloride （TTC） to measure infarct areas,immunofluorescence to observe p-JNK,p-p38 and cleaved cysteinyl aspartate-specific protease （Caspase）-3 in brain tissue,and Western blotting to detect the protein expression of p-JNK and p-p38.Results As compared with the I/R group,the neurological deficit score,the brain water content and the cerebral infarct size were significantly decreased in Dex group [2.86±0.45 vs.2.16±0.63,（85.23±1.19）% vs.（79.16±1.50）%,（28.53±1.68）% vs.（20.09±1.62）%,F=136.500,P=0.000;F=162.777,P=0.000;F=707.707,P=0.000].As compared with the I/R group,the number of cells expressing p-p38 （32.33±3.01 vs.18.67±2.73,F=210.481,P=0.000）,p-JNK （35.33±3.20 vs.17.83±2.48,F=257.534,P=0.000） and cleaved Caspase-3 （51.50±3.62 vs.33.00±3.58,F=346.888,P=0.000） was significantly redcued in Dex group.As compared with I/R group,the protein expression of p-p38 （1.38±0.11 vs.2.08±0.19,F=190.834,P=0.000）,p-JNK （0.77±0.06 vs.1.31±0.08,F=514.4

关 键 词：右美托咪定 脑缺血 再灌注损伤 丝裂原激活蛋白激酶类 

分 类 号：R614[医药卫生—麻醉学]