Attenuation of ischemia-reperfusion injury in the rat neocortex by the hydroxyl radical scavenger nicaraven.
Attenuation of ischemia-reperfusion injury in the rat neocortex by the hydroxyl radical scavenger nicaraven.
复制标题
羟自由基清除剂尼卡文减轻大鼠新皮质缺血再灌注损伤。
DOI：
10.1097/00006123-199702000-00027
复制
发表时间：
1997
期刊：
影响因子：
4.8
通讯作者：
Lee,KS
中科院分区：
文献类型：
--
作者：
Toyoda,T;Kassell,NF;Lee,KS
目的：氧自由基被认为是脑缺血再灌注损伤的重要因素。本研究的目的是研究羟基自由基清除剂（±）-N, N ' -丙烯丁尼丁酰胺（nicaraven）对局灶性脑缺血再灌注后脑损伤的影响。方法：将58只雄性Sprague-Dawley大鼠进行短暂性局灶性缺血，阻断颈动脉和大脑中动脉3小时。动物在缺血前10分钟（预处理）或后10分钟（处理后）开始连续输注尼卡拉文，剂量分别为20mg /kg /小时或60mg /kg /小时。用2% 2,3,5 -三苯四氮唑（n= 40）对冠状脑切片进行染色，评估梗死体积。在其他动物（n= 18）中，在缺血后1小时评估脑水肿。结果：nicaraven每小时20mg /kg的剂量引起梗死体积的小幅度减少（治疗前组和治疗后组分别为14.7%和12.3%）。以每小时60 mg/kg剂量的尼卡拉芬治疗可显著减少梗死体积（治疗前和治疗后分别减少18.6%[P< 0.05]和20.9%[P< 0.01]）。每小时服用60 mg/kg尼加拉瓜文的治疗前组和治疗后组的梗死面积减少没有显著差异。两种剂量的尼卡拉芬治疗后均可显著减少脑水肿。结论：本研究表明，在短暂局灶性缺血后的再灌注阶段，全身给予羟基自由基清除剂具有神经保护作用。据我们所知，该结果首次证明尼加拉瓜文对脑缺血-再灌注损伤有效，并证明再灌注过程中产生的氧自由基是缺血性脑损伤的重要触发因素。此外，研究结果表明，尼加拉瓜文可能是限制缺血性脑卒中后脑损伤的有用药物。
OBJECTIVE:Oxygen free radicals are considered important contributors to cerebral ischemia-reperfusion injury. The purpose of this study was to examine the effects of the hydroxyl radical scavenger,(±)-N, N′-propylenedinicotinamide (nicaraven), on cerebral injury after focal ischemia-reperfusion.METHODS:A total of 58 male Sprague-Dawley rats was subjected to transient focal ischemia by occluding both carotid arteries and one middle cerebral artery for 3 hours. Animals received continuous infusions of doses of 20 mg/kg per hour or 60 mg/kg per hour of nicaraven beginning either 10 minutes before (pretreatment) or immediately after (posttreatment) ischemia. Infarction volumes were evaluated by staining coronal brain sections with 2% 2, 3, 5-triphenyltetrazolium chloride (n= 40). In other animals (n= 18), brain edema was evaluated 1 hour after ischemia.RESULTS:A dose of 20 mg/kg per hour of nicaraven elicited small reductions in infarction volume (14.7 and 12.3% for the pre-and posttreatment groups, respectively). Treatment with a dose of 60 mg/kg per hour of nicaraven provided significant reductions in the volume of infarction (18.6%[P< 0.05] and 20.9%[P< 0.01] reductions for the pre-and posttreatment groups, respectively). The reductions in infarction size did not differ significantly between the pre-and posttreatment groups receiving a dose of 60 mg/kg per hour of nicaraven. Posttreatment with either dose of nicaraven significantly reduced brain edema.CONCLUSIONS:This study demonstrates the neuroprotective effects of a hydroxyl radical scavenger when administered systemically during the reperfusion phase after transient focal ischemia. The results provide, to our knowledge, the first evidence that nicaraven is effective against ischemia-reperfusion injury in the brain and demonstrate that oxygen free radicals generated during reperfusion are important triggers of ischemic brain damage. Furthermore, the findings suggest that nicaraven may be a useful agent in limiting brain injury after ischemic stroke.