炎性细胞因子在早期母子分离对成年后大鼠认知功能影响中的作用  

Effects of inflammatory factors and early maternal separation on the cognitive function in adult rats

作　　者：李丹丹 马芮 王茹 赵弘轶 黄勇华 Li Dandan;Ma Rui;Wang Ru;Zhang Hongyi;Huang Yonghua(The Second Clinical Medical College of Shanxi Medical University,Taiyuan 030001,China;Neurology Department,PLA Army General Hospital,Beijing 100700,China;Clinical Medical College of PLA Army General Hospital,Anhui Medical University,Beijing 100700,China;The Second Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]山西医科大学第二临床医学院,太原030001 [2]陆军总医院神经内科,北京100700 [3]安徽医科大学陆军总医院临床学院,北京100700 [4]陕西中医药大学第二临床医学院,咸阳712046

出　　处：《神经疾病与精神卫生》2018年第12期846-850,F0003,共6页Journal of Neuroscience and Mental Health

摘　　要：目的研究早期母子分离对成年雄性大鼠认知功能的影响,以及海马区炎性细胞因子在其中的作用,以探讨生命早期应激对神经发育影响的机制。方法新生SD大鼠随机分成母子分离组(MS组)和空白对照组(NMS组),MS组幼鼠在出生后第3~22天,每天与母鼠分离3h。NMS组不做处理。10周龄时,对两组成年大鼠进行Morris水迷宫行为学测试,NeuN免疫荧光染色观察两组大鼠海马齿状回(DG区)正常及变性神经元,GFAP/Iba-1免疫荧光染色观察星形胶质细胞和小胶质细胞,Ki67/DCX免疫荧光染色观察神经元增殖、分化情况,蛋白电泳法检测两组大鼠大脑海马区IL-1β、IL-6、TNF-α含量。结果相对于NMS组,行为学测试提示MS组大鼠学习、记忆能力下降,表现为MS组大鼠有更长的逃逸潜伏期,更少的目标象限停留时间和穿越平台次数(P<0.05);海马DG区正常及变性神经元的数目无明显变化(P>0.05),但星形胶质细胞及小胶质细胞的数目增加(P<0.01),且神经元增殖减少、分化减缓(P<0.01);海马区IL-1β、TNF-α表达增高(P<0.01),IL-6表达无明显变化(P>0.05)。结论生命早期重复母子分离能够引起大鼠海马区神经炎性反应,增加星形胶质细胞和小胶质细胞数目,增高海马区炎性细胞因子的表达,导致成年后大鼠认知功能的改变。Objective To explore the effects of early maternal separation on the cognitive function in adult male rats,and the involvement of inflammatory factors in hippocampus,to reveal the mechanistic role of early life stress in neuronal plasticity.Methods New born SD rats were randomly divided into maternal separation(MS)group and control(NMS)group.Maternal separation was carried out from Day 3 to Day 22,3 hours per day in MS group.There was no treatment in the NMS group.At the age of 10 weeks,Morris Water Maze was chosen to compare the behavioral deficits in adulthood between each group.NeuN immunofluorescent was used to calculate the normal neurons amounts in Dentate Gyrus(DG)rejion.GFAP/Iba-1 immunofluorescent was applied compare the amounts of astrocytes and microglias.Ki67/DCX immunofluorescent was select to observe the proliferation and differentiation of neurons in Dentate Gyrus,Western Blot was performed to detect the levels of IL-1β,IL-6 and TNF-α.Results Morris Water Maze findings showed that MS group rats had learning and memory declines,reflected by longer escape latency,less time in objective quadrant and fewer cross objective times(P<0.05)relative to NMS group rats.There was no significant change in the number of normal and degenerated neurons in DG region of hippocampus(P>0.05).However,the number of astrocytes and microglias increased(P<0.01).The expression of IL-1βand TNF-αin hippocampus increased(P<0.01),while the expression of IL-6 did not change significantly(P>0.05).Conclusions Repeated early life maternal separation could induce neuroinflammatory response in rat hippocampus.The increased the number of astrocytes and microglia and the increased expression of inflammatory cytokines in hippocampus lead to cognitive changes in adult rats.

关 键 词：大鼠 海马 应激 认知 炎性细胞因子 

分 类 号：R541.4[医药卫生—心血管疾病]