慢性间歇性低压低氧改善全脑照射造成的小鼠记忆认知功能障碍的研究  

Chronic intermittent hypobaric hypoxia improved the memory and cognitive impairment of mice with whole brain irradiation

作　　者：王媛[1] 刘宜先[2] 王帅[1] 张伟[1] 王祎[1] 武亚晶 王升[2] 王军[1] Wang Yuan;Liu Yixian;Wang Shuai;Zhang Wei;Wang Yi;Wu Yajing;Wang Sheng;Wang Jun(Department of Radiation Oncology,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Department of Physiology,Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学第四医院放疗科,石家庄050011 [2]河北医科大学生理教研室,石家庄050011

出　　处：《中华放射医学与防护杂志》2022年第7期487-492,共6页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的观察全脑照射后小鼠海马(CA)1区损伤的表现,探讨慢性间歇性低压低氧(CIHH)预处理对全脑照射后小鼠记忆认知功能的影响。方法采用完全随机法将48只成年雄性C57BL/6小鼠分为健康对照组、CIHH组、单纯照射组(IR)和CIHH+IR组。IR组采用6 MV X射线单次10 Gy全脑照射构建脑损伤模型。CIHH处理为小鼠在接受照射前置于低压氧舱预处理。Mirrors水迷宫实验观察小鼠逃避潜伏期、穿越平台次数以及目标象限停留时间,应用尼氏染色法观察海马CA1区神经元细胞的变化,应用免疫荧光法检测小鼠神经元前体细胞的微管相关蛋白(DCX)在海马齿状回(DG)颗粒下区(SGZ)的表达来评价神经发生情况。结果全脑照射后30 d,IR组与健康对照组相比,小鼠逃避潜伏期延长,穿越平台次数减少(P<0.001),目标象限内探索时间减少(P<0.001)。X射线引起小鼠CA1区神经元细胞排列紊乱、神经元细胞变性、坏死,小鼠CA1区DCX表达量明显减少。与IR组比较,CIHH+IR组可使小鼠逃避潜伏期缩短,穿越平台次数增加[(2.08±0.26)次vs.(0.83±0.24)次,P<0.001],目标象限内探索时间增加[(14.12±0.82)s vs.(7.42±0.73)s],P<0.001]。小鼠CA1区神经元变形、坏死减少,排列紊乱改善,CA1区DCX表达量增加。结论CIHH预处理对放射性海马损伤起到一定保护作用。Objective To observe the changes in hippocampus(CA1)and study the effect of chronic intermittent hypobaric hypoxia(CIHH)preconditioning on the memory and cognitive function of mice exposed to the whole brain irradiation.Methods A total of 48 C57BL/6 male mice were randomly divided into control group,CIHH group,irradiation group(IR group)and CIHH+IR group.For IR group,the whole brain of mice were irradiated with 10 Gy of 6 MV X-rays in a single fraction.Pretreatment with CIHH was performed by placing mice in a hypobaric chamber before radiation.The mirrors water maze experiment was performed in the four groups to observe the escape latency,the number of crossing platforms and the target quadrant residence time.Nissl staining was used to observe the changes of neuronal cells in hippocampal CA1 region.Immunofluorescence was used to detect the expression of microtubule-associated protein cells(DCX)in the subgranular zone(SGZ)of hippocampal dentate gyrus(DG)to evaluate neurogenesis.Results After 30 days of whole brain irradiation,the escape latency of mice prolonged gradually,the frequency of crossing platform decreased(P<0.001),and the exploration time in the target quadrant decreased(P<0.001).Xray irradiation caused disorder of mice neuronal cells,degeneration and necrosis of neuronal cells,and decrease of DCX expression in CA1 region of mice.Compared with IR group,the CIHH+IR group had shortened the escape latency,increased the frequency of crossing platform[(2.08±0.26)vs.(0.83±0.24),P<0.001],and also increased the exploration time in the target quadrant[(14.12±0.82)s vs.(7.42±0.73)s,P<0.001].Pretreatment with CIHH also alleviated the deformation and necrosis of neurons in hippocampus,and increased DCX expression in CA1 region.Conclusions Pretreatment of mice with CIHH plays a protective role in radiation induced hippocampal injury.

关 键 词：慢性间歇性低压低氧 全脑照射 小鼠海马 逃避潜伏期 神经发生 

分 类 号：R818.8[医药卫生—放射医学]