Abstract: Objective To evaluate the inhibition of the glutamate receptor blocker(GYKI52466) on the apoptosis of hypoxic ischemic encephalopathy(HIE) newborn rats' nerve cells. Methods In vivo:The newborn rats are randomly divided into blank control group (N),hypoxicischemic brain damage group (H) and GYKI52466 intervention group (G).Drug was given after modeling,the rats' neurological abnormality and ultrastructural change were observed of each group.In vitro:The newborn rat's brain cells were made into unicellular suspension liquid and cultivated for 4 days.Then group N cells were cultivated in normal environment,group H cells were cultivated in oxygen-glucose deprivation(OGD) environment,and group G cells were added with GYKI52466 after cultivated in OGD environment.After 6 hours,compared the cells growth state of each group,and analyzed the apoptosis of brain cells by flow cytometric. Results In vivo:The neurological behavior observation showed that group G cells' neurological abnormality was improved than group H cells;the electron microscopy observation showed,group H cells' neurons nuclei structure was damaged,nuclear membrane was ruptured,and nucleoli had mild shrinks.But group G cells' structure tended to be completed.In vitro:compared with model groups,the GYKI52466 treatment group's apoptotic cells were fewer,the numerical value had extremely significant difference (P<0.001). Conclusions Glutamate receptor blocker GYKI25466 can effectively reduce the abnormal neural behavior performance and pathology change for newborn rat with HIE,inhibit the apoptosis of HIE newborn rats' nerve cells.This test confirmed that GYKI25466 has neuroprotective effects on brain cells.

Key words: hypoxic-ischaemic encephalopathy, glutamate, AMPA, GYKI52466

摘要： 目的 探讨谷氨酸受体阻滞剂(GYKI52466)对缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)新生大鼠脑细胞凋亡的抑制作用。 方法 体内实验:将新生大鼠随机分为空白对照组(N组)、缺氧缺血性脑损伤组(H组)与GYKI52466干预组(G组)。造模后给药,观察各组大鼠的神经行为学异常及超微结构变化。体外实验: 将各组新生大鼠的脑细胞制成单细胞悬液,培养4 d后,N 组给予正常环境培养,H组给予缺氧缺糖环境,G组给予缺氧缺糖环境后添加GYKI52466培养,6 h后比较各组细胞生长状态,采用流式细胞仪进行脑细胞凋亡分析。 结果 体内实验:神经行为学观察,G组与H组相比,异常神经行为学有所改善;电镜下观察,H组神经元细胞核结构破坏,核膜破裂、核仁轻度皱缩,而G组结构趋向完整。体外实验:与模型组相比,G组的细胞凋亡数明显减少,数值差异有高度统计学意义(P<0.001)。 结论 谷氨酸受体阻滞剂GYKI25466有效的减轻新生大鼠缺氧缺血性脑病时异常的神经行为学表现和病理学改变,抑制神经细胞细胞凋亡,证实GYKI25466具有一定的神经保护作用。

关键词: 缺氧缺血性脑病, 谷氨酸, AMPA, 谷氨酸受体阻滞剂