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、RCI、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。
Abstract
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 min by four-vessel occlusion. Edaravone（3 mg·kg-1was 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（MPOand the content of malondialdehyde（MDAin 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 hippocampal 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，OPR. 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
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Key words
edaravone /
global brain ischemia /
4-vessle occlusion /
mitochondria
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高梅 时丽丽 张恒艾 陈柏年 王巧云 玄昭红 杜冠华.
依达拉奉对大鼠急性全脑缺血再灌注损伤的治疗作用[J]. 中国药学杂志, 2011, 46(12): 932-936
GO Mei;SHI Li-li;ZHNG Heng-i;CHEN i-nin;WNG Qio-yun;XUN Zho-hong;DU Gun-hu.
Therapeutic Effect of Edaravone in Transient Global Brain Ischemia/Reperfusion Rats[J]. Chinese Pharmaceutical Journal, 2011, 46(12): 932-936
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参考文献
［1］ YOSHIDA H，YANAI H， NAMIKI Y， et al. Neuroprotective effects of edaravone： a novel free radical scavenger in cerebrovascular injury［J］. CNS Drug Rev，2006，12（1： 9-20.
［2］ DING HY，DONG Q. The therapeutic effects of free radical scavenger edaravone on cerebral ischemia［J］. Cerebrovasc Dis Foreign Med Sci（国外医学：脑血管疾病分册，2004，12（7： 491-493.
［3］ ZHANG N，KOMINE-KOBAYASHI M，TANAKA R，et al. Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain［J］. Stroke，2005，36（10：2220-2225.
［4］ HU H T，WU J M，WANG S. Neuroprotective effect of edaravone on focal cerebral ischemia in rats［J］. Chin Pharm J（中国药学杂志，2005，40（19：1463-1466.
［5］ YAMAMOTO Y，YANAGISAWA M，TAK N W，et al. Repeated edaravone treatment reduces oxidative cell damage in rat brain induced by middle cerebral artery occlusion［J］. Redox Rep，2009，14（6：251-258.
［6］ PULSINELLI W A，BRIERLEY J A. A new model of bilateral hemispheric ischemia in the unanesthetized rat［J］. Stroke，1979，10（3：267-272.
［7］ LEMAY D R，GEHUA L，ZELENOCK G B，et al. Insulin administration protects neurologic function in cerebral ischemia in rats［J］. Stroke，1988，19（11：1411-1419.
［8］ SUN R，YI Y P，LV L L，et al. Effects of paeoniflorin on pathological changes in global brain ischemia model rats［J］. China J Chin Mater Med（中国中药杂志，2007，32（23： 2518-2522.
［9］ GUANG H M，DU G H. Protections of pinocembrin on brain mitochondria contribute to cognitive improvement in chronic cerebral hypoperfused rats［J］. Eur J Pharmacol，2006，542（1-3： 77-83.
［10］ ROBERTSON C L，SCAFIDI S，MCKENNA M C，et al. Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury［J］. Exp Neurol，2009，218（2： 371-380.
［11］ YANG J，LIU M，ZHOU J，et al. Edaravone for acute intracerebral haemorrhage［J］. Cochrane Database Syst Rev，2011，16（2：CD007755.
［12］ YAMAZAKI K，MIWA S，TOYOKUNI S. Effect of edaravone，a novel free radical scavenger，supplemented to cardioplegia on myocardial function after cardioplegic arrest： in vitro study of isolated rat heart［J］. Heart Vessels，2009，24（3：228-235.
［13］ YAGI K，KITAZATO K T，UNO M， Edaravone，a free radical scavenger，inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator［J］. Stroke，2009，40（2：626-631.
［14］ GAO M，LIU R，DU G H. Therapeutic strategies for stroke： targeting the neurovascular unit［J］. Chin J Clin Pharmacol Ther（中国临床药理学与治疗学杂志，2008，13（7： 813-821.
［15］ ROBERTSON C L，SCAFIDI S，MCKENNA M C，et al. Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury［J］. Exp Neurol，2009，218（2： 371-380.
［16］ YAMASHITAA A，OZAKIA A，IKEGAMIA A，et al. Effects of a new diphenylpiperazine calcium antagonist，KB-2796，on cerebral ischemic neuronal damage in rats［J］. Gener Pharmacol，1993，24（6： 1473-1480.
［17］ WANG Q S，ZHOU J N，XU T L， et al. A phospholipase C inhibitor，phenylmethyl- sulfonyl fluoride，ameliorates ischemic injury to brain mitochondria in rats［J］. Acta Pharmacol Sin（中国药理学报，2001，22（3： 249-252.
［18］ JEEVARATNAM K， VIDYA S. In vitro and in vivo effects of methyl isocyanate on rat brain mitochondrial respiration［J］. Arch Environ Contam Toxicol，1994，27（2： 272-275.
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