CAJ | 학술논문

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.
목적 통과간헐성저양궤제건립불동정도、불동시정적수면호흡잠정저통기종합정저양모식동물모형,관찰동물해마c -fos단백급조망적변화,탐토만성간헐성저양(chronic intermittent hypoxia group,CIH)대신경계통손상적궤제.방법 장72지성년웅성Wistar대서수궤균분위5％ CIH조(저양상태적양체적분수강지5％)、10％CIH조(저양상태적양체적분수강지10％)화공백대조조,분별우간헐저양제2、4、6、8주후채용면역조화법검측해마c-fos단백표체수평；TUNEL법검측해마신경원조망정황.결과 CIH조해마신경세포c-fos단백상대표체량급조망지수재2、4、6、8주균다우공백대조조(F치분별위44.52、57.56、24.20화13.18,P치균＜0.05),차5％CIH조c-fos단백표체량급조망지수균다우10％CIH조(P치균＜0.05)；불동정도CIH조c-fos단백표체급조망지수균유명현적시간차이성,균수시간적연장,선승고후강저,6주체도고봉,8주축점하강(P치균＜ 0.05).공백대조조c-fos단백표체급조망지수무시간차이성(P치균＞0.05).5％CIH조화10％CIH조c-fos단백적양성표체상대치여신경원조망지수정정상관(r치분별위0.816화0.701,P치균＜0.01).결론 중、중도간헐저양가인기대서해마신경세포c -los단백과도표체,진이도치신경세포조망,저가능시간헐저양조기뇌손해형성적중요궤제.
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.