抗肿瘤坏死因子抗体减轻小鼠短暂性脑缺血损伤

脑缺血后肿瘤坏死因子的表达明显增加。本研究将中和性抗肿瘤坏死因子单克隆抗体注入脑室内，以观察阻断内源性肿瘤坏死因子过度表达对小鼠短暂性脑缺血损伤的影响。小鼠随机分为对照组和抗肿瘤坏死因子抗体组，每组８只。脑缺血和再灌流均通过监测脑血流证实。将中和性单克隆Ｈａｍｓｔｅｒ抗小鼠肿瘤坏死因子抗体或对照载体在恢复再灌时立即注入脑室。小鼠大脑中动脉阻塞１ｈ再灌流２３ｈ断头取脑。脑梗塞体积测定用常规ＨＥ染色和计算机图象分析。以血管外内源性白蛋白免疫组化染色检测血脑屏障的损伤。对照组和肿瘤坏死因子抗体治疗组在脑缺血和再灌后脑血流无显著差异（Ｐ＞０．０５）。抗肿瘤坏死因子抗体组脑梗塞体积和血脑屏障损伤体积较对照组明显减小。阻断内源性肿瘤坏死因子能显著减少小鼠暂时性脑缺血脑梗塞体积和血脑屏障损伤体积（Ｐ＜０．０５）。脑梗塞体积的减小和血脑屏障损伤体积的减小相对应。提示内源性肿瘤坏死因子能加重暂时性脑缺血损伤。

ANTITNF ANTIBODY REDUCES ISCHEMIC BRAIN DAMAGE AFTER TEMPORARY MIDDLE CEREBRAL ARTERY OCCLUSION IN MICE

Previous studies have demonstrated that tumor necrosis factor alpha (TNF) was overexpressed following ischemic insult.We investigated the effect of blocking endogenous TNF on ischemic brain damage by intracisternal administration of monoclonal antiTNF monoclonal antibody after temporary middle cerebral artery occlusion (tMCAO) in mice.Mice were divided into control group and antiTNF mAbtreated group.There were eight mice in each group.Middle cerebral artery was temporarily occluded in CD1 mice for 1 h followed by 23 h reperfusion.Ischemia and reperfusion were confirmed by measuring cerebral blood flow.Neutralizing monoclonal hamster antimouse TNF monoclonal antibody(antiTNF mAb) or vehicle was administered intracisternally immediately at the onset of reperfusion.The infarct volume was measured by routine HE staining and image analysis.The disruption of bloodbrain barrier was determined by immunostaining of extravasated endogenous albumin.Results showed that there was no significant difference in cerebral blood flow after middle cerebral artery occlusion and reperfusion between the two groups.The infarct volume and bloodbrain barrier disruption volume were significantly smaller in the antiTNF mAbtreated group than the control group(P<005). The reduction of infarct volume mirrors the attenuation of BBB disruption. Our results suggested that overexpression of endogenous TNF might exacerbate the brain injury after temporary middle cerebral artery occlusion.