Memantine对新生大鼠缺氧缺血性脑损伤的影响

Effect of Memantine on hypoxic-ischemic brain damage in neonatal rats and its mechanism

目的 :研究美金胺 (Memantine)对新生大鼠缺氧、缺血性脑损伤 (HIBD)脑保护作用及机制。方法 :应用新生 7日龄 Wistar大鼠随机分为假手术组、HIBD组、Memantine治疗组 ,采用结扎左侧颈总动脉并吸入 8% O2 +92 % N2 混合气体制成新生大鼠 HIBD动物模型。于 HIBD后即刻腹腔注射 Mem antine 2 0 mg/ kg或等量生理盐水 ,4 8h后处死 ,用放射免疫法测血清 NSE水平 ,用硝酸还原酶法测血清 NO水平 ,用 H - E染色观察脑组织病理变化。结果 :Memantine可使脑组织病理改变明显减轻 ,可降低血清中 NSE浓度 ,可降低血清中 NO浓度。结论 :Memantine对脑缺氧缺血损伤具有脑保护作用 ;Mem an-tine通过阻断 NMDA受体减少毒性 NO的生成 ,是其脑保护作用可能机制之一。

Objective: To explore the effect of Memantine on hypoxic-ischemic brain damage(HIBD) in neonatal rats and its mechanism. Methods: The HIBD models were established with 7-day postnatal Wistar rats and divided into three groups,namely control group ,HIBD group and Memantine treated group.HIBD models were prepared by permanent ligation of left common carotid artery combined with a temporary systemic hypoxia (inhaling 8%O 2+92%N 2). Right after hypoxic-ischemic damage ,Memantine or normal saline solution was injected intraperitoneally(20mg/kg). 48 hours after hypoxic-ischemic damage, nitrate reductase method was used to measure serum nitric oxide (NO) contents .Values of serum neuron-specific enolase(NSE) were measured by radioimmunoassay. Hematoxylin and eosin stain(H-E) was used to observe the pathological changes in cerebral tissues . Results: Memantine significantly reduced the pathological changes in cerebral tissues. and lowered NSE contents and NO contents in serum. Conclusion: It is suggested that intraperitoneal administration of Memantine can protect against hypoxic-ischemic brain damage in neonatal rats.Memantine: inhibits production of toxic NO by blocking NMDA receptor,which is its possible protective mechanism for HIBD.