油酰乙醇胺在小鼠急性局灶性脑缺血再灌注损伤中的作用及机制  

The protective effect of oleoylethanolamide on acute focal cerebral ischemia/reperfusion injury in mice and its mechanism

作　　者：刘金凤[1] 周宇[2] 杨武双[3] 马昂[2] 郑城微[2] 励佳忆[2] 金鑫[2] 

机构地区：[1]厦门市中医院药剂科 [2]厦门大学医学院基础医学部 [3]厦门市中医院神经外科,福建厦门361009

出　　处：《中国生化药物杂志》2012年第6期758-761,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：厦门市科技计划资助项目(NO.3502Z20084022)

摘　　要：目的研究油酰乙醇胺(OEA)在脑缺血再灌注损伤中的作用及机制。方法线栓法制备小鼠大脑中动脉栓塞模型,缺血90 min后再灌注。应用HPLC-MS/MS方法测定脑组织内OEA的含量。给予OEA(5,10,40 mg/kg,ig)或OEA水解酶抑制剂URB597(1 mg/kg,ig),观察其对小鼠急性脑缺血再灌注损伤的影响。测定脑组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)及过氧化氢酶(CAT)的活性。观察MK886对OEA抗脂质过氧化损伤的影响。结果脑缺血再灌注后6 h,损伤侧脑内OEA含量开始升高,再灌注后24 h升高最明显。脑缺血再灌注后给予OEA(40 mg/kg)或URB597(1 mg/kg)可减少神经功能缺失评分,减小脑梗死体积,减轻脑水肿程度。OEA可减少脑内MDA含量,增加抗氧化酶SOD的活性。OEA这一抗氧化作用可被MK886所取消。结论脑缺血再灌注可增加脑内OEA的含量,OEA通过激动PPARα,减轻脂质过氧化损伤发挥抗脑缺血再灌注损伤作用。Purpose To investigate the role of oleoylethanolamide （OEA） in focal cerebral ischemia reperfusion injury, and to illustrate its possible mechanisms. Methods Focal cerebral ischemia was in- duced by middle cerebral artery occlusion in mice for 90 rain and then reperfusion. The contents of OEA in brain tissue following cerebral ischemia reperfusion were measured by HPLC-MS/MS. OEA（5,10,40 mg/kg） and URB597（ 1 mg/kg） were intragastrically administered at the same time of reperfusion and2 h after reperfusion respectively. The neurological deficit score, infarct volume and brain edema degree were determined 24 h after reperfusion. The contents of maiondialdehyde （MDA） and the activity of super- oxide dismutase（SOD） and catalase（CAT） in brain tissue were measured. Results OEA content in brain tissue increased 6 h after reperfusion and markedly increased 24 h after reperfusion. OEA （40 mg/kg） and URB597 （1 mg/kg） ameliorated neurological dysfunction,reduced infarct volume, attenuated brain e- dema degree and decreased the extravasations of EB. OEA （40 mg/kg） increased the activity of SOD and attenuated the lipid peroxidation in brain tissues. MK886 abolished this anti-oxidant effect of OEA. Con- clusion The content of OEA in brain tissue increased following focal cerebral ischemia reperfusion in mice. OEA exerts protective effect against acute focal cerebral ischemia reperfusion injury by activating PPARct and reducing lipid peroxidation in brain tissue.

关 键 词：油酰乙醇胺 脑缺血 再灌注损伤 脂质过氧化 

分 类 号：R961[医药卫生—药理学]