不同程度慢性间歇低氧对大鼠海马C-fos蛋白及凋亡的影响  

Influence of different degrees of chronic intermittent hypoxia on c-fos protein and apoptosis in rats

作　　者：李琳[1] 王红阳[1] 陈宝元[2] 张盼盼[1] 韩晓庆[1] 雷军旗[1] 杨林[1] 

机构地区：[1]河北联合大学附属医院呼吸科,唐山063000 [2]天津医科大学总医院呼吸科

出　　处：《中华耳鼻咽喉头颈外科杂志》2012年第2期117-121,共5页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：河北省高等学校科学技术研究重点项目（ZH2011120）

摘　　要：目的 通过间歇性低氧机制建立不同程度、不同时程的睡眠呼吸暂停低通气综合征低氧模式动物模型,观察动物海马c -fos蛋白及凋亡的变化,探讨慢性间歇性低氧（chronic intermittent hypoxia group,CIH）对神经系统损伤的机制.方法 将72只成年雄性Wistar大鼠随机均分为5％ CIH组（低氧状态的氧体积分数降至5％）、10％CIH组（低氧状态的氧体积分数降至10％）和空白对照组,分别于间歇低氧第2、4、6、8周后采用免疫组化法检测海马c-fos蛋白表达水平；TUNEL法检测海马神经元凋亡情况.结果 CIH组海马神经细胞c-fos蛋白相对表达量及凋亡指数在2、4、6、8周均多于空白对照组（F值分别为44.52、57.56、24.20和13.18,P值均＜0.05）,且5％CIH组c-fos蛋白表达量及凋亡指数均多于10％CIH组（P值均＜0.05）；不同程度CIH组c-fos蛋白表达及凋亡指数均有明显的时间差异性,均随时间的延长,先升高后降低,6周达到高峰,8周逐渐下降（P值均＜ 0.05）.空白对照组c-fos蛋白表达及凋亡指数无时间差异性（P值均＞0.05）.5％CIH组和10％CIH组c-fos蛋白的阳性表达相对值与神经元凋亡指数呈正相关（r值分别为0.816和0.701,P值均＜0.01）.结论 中、重度间歇低氧可引起大鼠海马神经细胞c -los蛋白过度表达,进而导致神经细胞凋亡,这可能是间歇低氧早期脑损害形成的重要机制.Objective To establish different degrees and duration of animal hypoxia model of sleep apnea hypopnea syndrome according to the mechanism of intermittent hypoxia,to observe the effect of c-fos protein and apoptosis,and to explore the mechanism of nervous system injury.Methods By using the model of chronic intermittent hypoxia in rats,male Wistar rats （ n =72 ） were randomly divided into three groups：5% of chronic intermittent hypoxia group （the fraction of oxygen volume reduced to 5% under hypoxia）,10% of chronic intermittent hypoxia group （ the fraction of oxygen volume reduced to 5% under hypoxia） and control group.The levels of on c-fos protein and apoptosis of hippocampal cell in three groups were detected at the 2nd,4th,6th and 8th week respectively.The expression of c-fos protein in hippocampal cell was detected by immunohistochemical method and the apoptosis of hippocampal cell was detected by TUNEL.Results The relative quantity of c-fos protein and apoptotic index in CIH groups were significantly higher than that of the control group on the 2nd,4th,6th and 8th weeks （ F were 44.52,57.56,24.20and 13.18,P 〈0.05）,and these were higher obviously in 5% CIH group than that in 10% CIH group （P 〈 0.05）.The expression of c-fos protein and apoptotic index in two CIH groups was different depending upon the different degree and duration of chronic intermittent hypoxia.With increased exposure time,the expression of c-fos protein and apoptotic index was high generally at first,peaked at 6th week,then down at 8th week （P 〈0.05）.While it in UC group was invariability in different time（P 〉0.05）.The correlation between the relative quantity of c-fos protein and apoptotic index in two CIH groups was positive （r were 0.816 and 0.701,P 〈 0.01 ）.Conclusion Moderate and severe intermittent hypoxia induced the excessive expression of c-fos protein in hippocampus,caused nerve cell apoptosis,and may play an important ro1e in the mechanism of early brain injury of intermittent hypoxia.

关 键 词：缺氧 海马 原癌基因蛋白质C-FOS类 细胞凋亡 睡眠呼吸暂停综合征 

分 类 号：R56[医药卫生—呼吸系统]