急性脑缺血大鼠鼻腔给予rhEPO治疗后脑组织中Ngb和TNF-α的表达

Expression of Ngb and TNF-α in Rat with Acute Cerebral Ischemia by Intranasal Administration of Recombinant Human Erythropoietin

目的鼻腔给予脑缺血大鼠重组人促红细胞生成素(rhEPO),通过分析脑组织中肿瘤坏死因子α(TNF-α)和神经球蛋白(Ngb)的表达情况,探讨其对急性脑缺血的神经保护作用及机制。方法将54只健康雄性SD大鼠随机分为对照组、模型组、rhEPO治疗组,每组18只。采用Zea-Longa改良线栓法[1]制备大鼠永久性局灶性脑缺血(pMCAO)模型。rhEPO治疗组在缺血1h鼻腔给予小剂量rhEPO(48U/40μL),模型组和对照组在缺血1h鼻腔给予等量的生理盐水。缺血24h后断头处死大鼠,取出完整脑组织,分别用干湿质量法计算脑组织含水量,TTC(2,3,5—氯化三苯基四氮唑)法测量脑梗死体积,免疫组织化学方法测定TNF-α与Ngb的表达。结果模型组与对照组相比,脑含水量明显增加,Ngb与TNF-α的表达增加,差异有统计学意义(P<0.05)。rhEPO治疗组与模型组相比,脑含水量下降,梗死面体减小,TNF-α的表达下降,Ngb的表达增加,差异有统计学意义(P<0.05)。结论鼻腔给予rhEPO是一种有效的给药途径,其可能通过降低TNF-α的表达和促进Ngb的表达来发挥神经保护作用。

Objective To investigate the expression of neuroglobin（Ngb） and tumor necrosis factor-α（TNF-α） in the rat with acute cerebral ischemia brain after intranasal administration of recombinant human erythropoietin（rhEPO）.Methods Fifty-four healthy male Sprague-Dawley（SD） rats were randomly divided into three groups：Control group（n=18）,model group（n=18） and rhEPO treatment group（n=18） given 48 U rhEPO via intranasal administration after ischemia for 1 hour.The models were established by suture of middle cerebral artery.All rats were decapitated after ischemia for 24 hours,the water contents in the brain tissues were calculated by dry-wet weight method,the infarction volume was measured by 2,3,5-triphenyl tetrazolium chloride（TTC） staining,and the expression of Ngb and TNF-α were detected by immunohistochemistry.Results Compared with control group,the brain tissue water content was increased and the expression of Ngb and TNF-α were increased in model group.Compared with model group,the brain tissue water content was diminished,the volume of infarction was reduced,the expression of TNF-α was decreased,and the expression of Ngb was increased in rhEPO treatment group.Conclusion Intranasal administration of rhEPO was an effective drug application method.Its neuroprotective effect might be related to the reduction of expression of TNF-α and elevation of expression of Ngb.