高原脑水肿小鼠模型的建立与鉴定  

Establishment and Evaluation of a Mice Model of High-Altitude Cerebral Edema

作　　者：春花[1] 白玛康卓[1] CHUNHUA;BAIMAKANGZHUO(Medical College of Tibet University,Lhasa 850000,China)

机构地区：[1]西藏大学医学院,拉萨850000

出　　处：《四川大学学报（医学版）》2023年第6期1269-1275,共7页Journal of Sichuan University(Medical Sciences)

基　　金：藏才预指[2022]1号中央支持地方珠峰学者人才发展支持计划-青年博士发展计划(No.zdbs202213);西藏自治区科技厅重点研发与转化项目(No.XZ202101ZY0009G)资助。

摘　　要：目的 建立高原脑水肿(high altitude cerebral edema, HACE)动物模型,探寻能导致明显HACE临床表征的海拔条件,为进一步研究HACE的发病机制和干预策略奠定基础。方法 选取8周龄雄性BALB/c小鼠,分为对照组(Control)和HACE组。Control组常压常氧处理(10只);HACE组置于低压低氧舱内,模拟4 000 m、5 000 m、6 000 m海拔高度,分别处理6 h、12 h、24 h、48 h、72 h,每个海拔高度每时点处死10只。HE染色观察脑组织形态学改变,以选择合适的模拟海拔建立显著的HACE模型并鉴定造模结果。HACE模型鉴定方法:称重检测脑水肿,Evans blue(EB)检测血脑屏障(brain-blood barrier, BBB)通透性、免疫荧光染色检测细胞凋亡情况。结果 海拔4 000 m和5 000 m时无小鼠死亡,海拔6 000 m时小鼠死亡率为12.2%。HE染色显示脑组织形态和结构在海拔4 000 m无明显改变;在海拔5 000 m的48 h、72 h组可见少许脑细胞水肿。海拔6 000 m构建的HACE模型最为显著,各组HE染色均出现脑细胞体积增大、肿胀,以24 h、48 h、72 h为甚,并出现细胞排列紊乱、间隙增大及核固缩;模型鉴定示海拔6 000 m构建的HACE模型小鼠脑水肿和EB通透率12 h后增加,各时点无明显细胞凋亡。结论 用低压低氧舱模拟海拔6 000 m(气压47.19 kPa、氧分压9.73 kPa)可有效建立HACE模型。Objective To establish an animal model of high-altitude cerebral edema(HACE),to explore the altitude and oxygen partial pressure conditions that can lead to obvious clinical manifestations of HACE,and to lay the foundation for further research of the pathogenic mechanisms and intervention strategies of HACE.Methods Male BALB/c mice of 8 weeks old were randomly assigned to Control and HACE groups.The Control group(n=10)was treated with normobaric and normoxic conditions,while the HACE groups were placed in hypobaric hypoxic(HH)chambers for the durations of 6 h,12 h,24 h,48 h and 72 h,respectively,receiving treatments of simulated HH conditions at the altitudes of 4000 m(n=10 for each group receiving different durations of HH treatment),5000 m(n=10 for each group receiving different durations of HH treatment),and 6000 m(n=10 for each group receiving different durations of HH treatment).HE staining was performed to observe the morphological changes of the brain tissue and the appropriate simulated altitude conditions were selected accordingly for the construction and evaluation of the best HACE model.The HACE model was evaluated in the following ways,the mouse brain was weighed and the cerebral edema was measured accordingly,Evans blue(EB)was injected to determine the permeability of the blood-brain barrier(BBB),and the cell apoptosis was determined by immunofluorescence staining.Results There were no deaths in the groups treated with the HH conditions of the altitudes of 4000 m and 5000 m,while the mortality in the 6000 m altitude treatment groups was 12.2%.HE staining showed no significant changes in brain morphology or structure in the group receiving HH treatment for the altitude of 4000 m.A small amount of brain cell edema was observed in the groups receiving 48 h and 72 h of HH treatment for the altitude of 5000 m.The groups receiving HH treatment for the altitude of 6000 m demonstrated the most prominent modeling effect.HE staining showed increased volume and swelling of brain cells in all the 6000 m groups,e

关 键 词：高原反应 高原脑水肿 血脑屏障 低压低氧 

分 类 号：R594.3[医药卫生—内科学] R-332[医药卫生—临床医学]