依达拉奉对大鼠急性全脑缺血再灌注损伤的治疗作用  

Therapeutic Effect of Edaravone in Transient Global Brain Ischemia/Reperfusion Rats

作　　者：高梅[1] 时丽丽[1] 张恒艾[1] 陈柏年[1] 王巧云[2] 玄昭红[1] 杜冠华[1] 

机构地区：[1]中国医学科学院药物研究所国家药物筛选中心,北京100050 [2]山东滨州医学院药学院,山东滨州256603

出　　处：《中国药学杂志》2011年第12期932-936,共5页Chinese Pharmaceutical Journal

基　　金：卫生部公益性行业科研专项(200802041200802038)

摘　　要：目的评价依达拉奉对大鼠全脑缺血再灌注损伤的治疗作用,为其在临床的应用提供实验依据。方法采用大鼠四动脉阻断(4VO,20 min)制备全脑缺血再灌注模型,用尼氏染色方法考察依达拉奉注射液对海马CA1区神经元病理损伤的影响,生化方法进行脑组织中氧化-抗氧化指标的测定,线粒体氧耗测定仪进行脑线粒体呼吸功能的评价。结果依达拉奉(3 mg·kg-1,iv)对于大鼠全脑缺血再灌注后脑海马CA1区神经元的形态及数量均有显著改善作用;可显著抑制氧化应激导致的脑组织中超氧化物歧化酶(SOD)的活性改变,降低丙二醛(MDA)、NO、髓过氧化物酶(MPO)的含量;显著提高线粒体NADH/FADH2呼吸链的ADP/O、V3、RC I、OPR,提高氧化磷酸化效率。结论依达拉奉通过抑制氧化应激、改善线粒体呼吸功能,从而发挥其对于大鼠全脑缺血再灌注损伤的保护作用。OBJECTIVE To evaluate the therapeutic effect of edaravone in transient global brain ischemia/reperfusion rats. METHODS Adult male Sprague-Dawley rats were subjected to global cerebral ischemia for 20 rain by four-vessel occlusion. Edara- vone （3 mg · kg^-1） was administrated intravenously 30 min after reperfusion. Histological examination by Nissl staining was employed to assess the neuronal injury after ischemia. The activities of superoxide dismutase （SOD）, myeloperoxidase （MPO）and the content of malondialdehyde（MDA） in brain tissue were tested by colorimetric assays. Respiratory activity of brain mitochondria was determined. RESULTS Edaravone significantly ameliorated neurological deficits and alleviated the degree of hippoeampal neuronal loss at 72 h after global cerebral I/R. Treatment with edaravone reduced the compensatory increase of SOD and MPO activity,and decreased the MDA level and NO activity. Edaravone also improved the respiratory activity of 4VO brain mitochondria, through increasing ADP/O, V3, RCI, 0PR. CONCLUSION Edaravone exert a therapeutic effect against global cerebral ischemic injury in rats by inhibiting oxidative stress and improving respiratory activity of mitochondria.

关 键 词：依达拉奉 全脑缺血 四动脉阻断 线粒体 

分 类 号：R965[医药卫生—药理学]