新生大鼠缺氧缺血性脑病时HIF-1α基因表达的变化  

Expression of HIF-1α in neonatal rats with hypoxic-ischemic encephalopathy (HIE)

作　　者：崔红[1] 杨爱君[1] 崔雁[1] 艾泉山[1] 叶卉初[1] 黄德庄[2] 兰孟东[3] 张万东 

机构地区：[1]首都医科大学附属北京友谊医院儿科,北京100050 [2]首都医科大学附属佑安医院,北京100053 [3]北京地坛医院,北京100011 [4]加拿大国家研究院生物研究所

出　　处：《临床和实验医学杂志》2007年第2期1-2,5,共3页Journal of Clinical and Experimental Medicine

基　　金：首都医科大学基础;临床合作基金(项目编号:2006jl18)

摘　　要：目的了解新生大鼠缺氧缺血性脑病(HIE)时低氧诱导因子-1α(HIF-1α)基因表达的变化,以期寻找更为有效治疗手段。方法24只7日龄新生SD大鼠,随机分成2组,假手术组和缺氧缺血组,根据处死时间点每组分成1d和3d两个小组,每组6只。缺氧缺血组结扎左颈总动脉后休息1h,再置于8%氧浓度的低氧环境中2h,分别于实验1d、3d乙醚麻醉下处死动物,留取脑组织,半数中性甲醛溶液固定,半数液氮保存,采用HE染色、逆转录聚合酶链反应(RT-PCR)和免疫组化,在蛋白和mRNA水平检测新生大鼠HIE时HIF-1α基因的表达。结果缺氧缺血组大鼠相继表现为烦躁不安、全身发绀,呼吸加深加快、站立不稳、嗜睡、激惹或间断发作的痉挛和抽搐;HE染色显示:左侧大脑皮层出现局灶性神经元核固缩、核碎裂、核仁偏位、不清或消失、基质疏松;脑组织HIF-1αmRNA表达较对照组增加,尤其是缺氧缺血3d组,但差异无统计学意义;免疫组化显示:缺氧缺血组1d组和3d组各时间点、各大鼠大脑皮层和海马区均可见不同程度的HIF-1α表达,明显高于假手术组(P=0.00),阳性表达主要在血管内皮细胞,海马和皮层的锥体细胞亦有HIF-1α阳性细胞分布。结论新生大鼠缺氧缺血性脑病时HIF-1基因表达增强,主要表现在大脑血管内皮细胞。Objective To get the message of expression of HIF - 1α in neonatal rats with hypoxic - iscbemic enoepbalopathy （HIE）, so to find out the more effective method to treat HIE. Methods Twenty four neonatal rats aged 7d were divided randomly into two groups, normal control group and hypoxic - ischemic group with 12 rats in each. According to the time point, 12 rats of every group were further divided randomly into two groups including 1d and 3d, with 6 rats in each subgroup. The left common carotid artery of the neonatal rats in hypoxic - isehemic group was ligated. 1 h later, they were subjected to inhalation of 8% oxygen for 2h. The expression of HIF —1α in the levels of protein and mRNA in brain tissues of the rats were determined with HE staining, immunohistochemical staining and RT - PCR. Results Neonatal rats in hypoxic - ischemic group behaved restlessness, cyanosis, deep and rapid breath, astasia, lethargy, irritation and spasm; There were focal pyknosis, fragmentation, dissymmetry, blur or disappearance of nucleoli ,raffias of ground substance in left cerebral cortex;The expression of HIF - 1αmRNA in brain tissue of hypoxic - ischemic group were higher than that in normal control group, especially hypoxic - ischemie group at 3d, but there was no statistic significance ; HIF —1α positive cells were found in cerebral cortex and hippocampus. There were more HIF - 1α positive cells in hypoxic - ischemic group（ p =0.00）and mainly in vascular endothelial cells （VECs）. Conclusion The expression of HIF—1α in brain tissue was up -regulated in neonatal rats with HIE, mainly in VECs.

关 键 词：低氧诱导因子-1Α 缺氧缺血性脑病 动物模型 大鼠 

分 类 号：R722.1[医药卫生—儿科]