椒苯酮胺对脑缺血再灌注大鼠认知障碍的影响  

Effects of piperphentonamine hydrochloride on cognitive deficits in rats induced by cerebral ischemia-reperfusion

作　　者：朱汉祎[1] 宾娟[1] 王闯[1,2] 林焕冰[1,3] 周恒[1] 徐江平[1] 

机构地区：[1]南方医科大学药学院药理学系,广东广州510515 [2]宁波大学医学院,浙江宁波315211 [3]广东省食品药品监督管理局审评认证中心,广东广州510080

出　　处：《南方医科大学学报》2011年第11期1858-1862,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30672453;30973518);"重大新药创制"科技重大专项"十二五"计划项目(2011ZX091011-003);广东省自然科学基金(7117782)~~

摘　　要：目的观察椒苯酮胺(piperphentonamine hydrochloride,PPTA)对脑缺血再灌注大鼠认知障碍的影响并探索其机制。方法随机将大鼠分为假手术组、模型组、PPTA组(2.5、5、10 mg/kg)和阳性对照依达拉奉组(6 mg/kg)。采用大鼠大脑中动脉闭塞2 h再灌注模型,缺血1 h后给药。脑缺血再灌注24 h后进行避暗实验。行为学测试后24 h,断头取脑,分离右侧缺血脑区,用RT-PCR方法检测IL-1β、TNF-α、Caspase-3及HSP-70的mRNA表达。结果避暗实验中,与假手术组相比,模型组动物认知能力显著性降低,而PPTA剂量依赖性地逆转了这一效应;伴随认知能力的下降,模型组动物炎症因子(IL-1β和TNF-α),凋亡因子Caspase-3及HSP-70 mRNA水平均显著性增高;与模型组比较,PPTA显著性降低了IL-1βmRNA,TNF-αmRNA,Caspase-3 mRNA及HSP-70 mRNA水平,而阳性对照药依达拉奉组未见对炎症因子产生显著影响。结论 PPTA可能通过改善脑缺血再灌注损伤后引起的炎症及凋亡反应,增加脑组织对缺血再灌注损伤应激的耐受性,从而发挥神经保护作用,可能是PPTA改善认知障碍的机制之一。Objective To investigate the effect of piperphentonamine hydrochloride（PPTA） on cognitive deficits induced by ischemia-reperfusion and explore the possible mechanisms.Methods SD rats were randomly divided into sham-operated group,ischemia-reperfusion group（with saline injection）,PPTA-treated groups（2.5,5,10 mg/kg） and edaravone-treated group（6 mg/kg）.Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion,and the agents were administrated 1 h after ischemia.At 24 h after ischemia,step-through passive avoidance test was carried out,and 24 h later IL-1β,TNF-α,caspase-3 and HSP-70 mRNA expressions in the ischemic brain tissues were measured with RT-PCR.Results In the step-through passive avoidance test,the rats in the ischemia-reperfusion group showed significantly shorter latency and more error times than those in the sham group,and these behavioral changes were improved significantly by treatments with PPTA and edaravone.Cerebral ischemia-reperfusion caused significantly increased expressions of IL-1β,TNF-α,caspase-3 and HSP-70 mRNA,and these changes were obviously reversed by PPTA,but not by edaravone.Conclusions PPTA can reverse cognitive deficits induced by cerebral ischemia-reperfusion probably by decreasing the inflammatory responses and cell apoptosis in the brain,suggesting its potential as a new therapeutic agent for improving the cognitive function following cerebral ischemia-reperfusion.

关 键 词：学习记忆 缺血再灌注 凋亡 炎症 椒苯酮胺 

分 类 号：R743.3[医药卫生—神经病学与精神病学]