环氧化酶2参与远隔缺血预适应对大鼠脑缺血再灌注损伤的保护作用  

Cyclooxygenase-2 is involved in the protective effects of remote ischemic preconditioning on ischemia-reperfusion injury in rats

作　　者：尹洁[1] 闫峰[1] 李森[1] 罗玉敏[1] 赵咏梅[1] 

机构地区：[1]首都医科大学宣武医院、北京市老年病医疗研究中心、神经变性病教育部重点实验室、脑血管病转化医学北京市重点实验室,100053

出　　处：《中国神经免疫学和神经病学杂志》2014年第3期166-169,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：北京市自然科学基金资助项目(7122036);省部共建国家重点实验室培育基地脑重大疾病实验室开放课题(2012NZDJ03);脑血管病转化医学北京市重点实验室开放课题(2013NXGZ03)

摘　　要：目的研究远隔缺血预适应(remote ischemic preconditioning,RIPC)对大鼠脑缺血再灌注损伤后神经功能评分、脑梗死体积以及环氧化酶2(cyclooxygenase-2,COX2)蛋白表达的影响,探讨RIPC对脑缺血损伤的保护作用及其相关机制。方法健康雄性SD大鼠24只,随机分为假手术组(Sham)、大脑中动脉梗死(middle cerebral artery occlusion,MCAO)组及RIPC+MCAO组3组,每组8只。MCAO组及RIPC+MCAO组使用线栓法制作大鼠MCAO模型,模拟缺血2h;其中RIPC+MCAO组在MCAO之前,采用夹闭双侧股动脉10min开放10min,每天3个循环的方法,给予大鼠连续3d的RIPC。3组大鼠均于再灌注24h时进行神经功能评分(Longa 5分法),采用TTC染色检测脑梗死体积,Western blotting法检测大脑梗死侧COX2蛋白表达。结果Sham组大鼠无脑梗死发生,Longa评分0分。再灌注24h时RIPC+MCAO组Longa评分(2.17±0.41)及脑梗死体积分数〔(41.77±10.83)%〕均低于MCAO组〔分别为3.33±0.58和(59.80±6.64)%〕(均P<0.05)。大鼠脑梗死侧COX2蛋白相对表达MCAO组(0.36±0.02)和RIPC+MCAO组(0.13±0.09)均高于Sham组(0.02±0.00;P<0.05),RIPC+MCAO组低于MCAO组(P<0.05)。结论 RIPC可以减轻大鼠脑缺血损伤,其机制可能与降低脑缺血再灌注大鼠脑内COX2蛋白表达水平有关。ABSTRACT： Objective To investigate the neurological scores, infarct volume, and expression changes of cyclooxygenase 2 （COX2） in ischemia-reperfusion rats with remote ischemic preconditioning （RIPC） in order to explore the protective effect of RIPC on cerebral ischemic injury and its mechanisms. Methods Twenty-four male Sprague Dawley rats were randomly divided into three groups： sham surgery group, middle cerebral artery occlusion （MCAO） group, and RIPC--MCAO group, there were 8 rats in each group. MCAO operation was performed by suture method in MCAO group and RIPC＋ MCAO group rats. The rats underwent right MCAO for 2 h. Three cycles of RIPC induced by temporarily occluding the bilateral femoral arteries （10 minutes） prior to 10 minutes of reperfusion were given once a day for 3 days before the RIPC--MCAO group rats received MCAO surgery. At 24 h after reperfusion, Longa score was used to evaluate neurological det＇icits of rats. Then, the brains were removed and dyed with 2, 3, 5-triphenyhetrazolium chloride （TTC） to measure the infarct percentage. The expression of COX2 protein in ipsilateral hemispheres was determined quantitatively by Western blotting analysis. Results In sham surgery group rats, the Longa score was 0 and no infarction was observed. The Longa score and infarct percentage in RIPC＋MCAO group [2.17±0.41 and （41.77±10.83）%] decreased significantly compared with those of MCAO group [3.33±0.58 and （59.80±6.64）5] （both P〈 0.05）. At 24 h after reperfusion, the expression of COX2 protein in ipsilateral hemispheres of MCAO group rats （0. 364±0.02） and RIPC＋MCAO group （0.13±0.09） increased significantly compared with that of sham group rats （0.02±0.00） （P〈 0.05） while the expression of COX2 protein in the RIPC＋ MCAO group decreased significantly compared with that of the MCAO group （P〈 0.05）. Conclusions RIPC in rat hindlimbs decreases cerebral ischemic injury. The underlying mechanism of RIPC may be reducing the expression

关 键 词：远隔缺血预适应 脑缺血 再灌注 脑损伤 环氧化酶2 

分 类 号：R743.3[医药卫生—神经病学与精神病学]