四川大学学报（医学版）2023，Vol.54Issue(6)：1269-1275,7.DOI:10.12182/20231160604
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
摘要
Abstract
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 4 000 m and 5 000 m,while the mortality in the 6 000 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 4 000 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 5 000 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 6 000 m groups,especially in the 24 h,48 h and 72 h treatment groups.In all the 6 000 m groups,cell arrangement disorder,gap enlargement,and nuclear contraction were observed.Evaluation of the modeling effect demonstrated that,in the HACE mice model constructed with the HH conditions for the altitude of 6 000 m,cerebral edema and EB permeability increased after 12 h HH treatment and there was no obvious apoptosis in the modeling groups receiving different durations of treatment.Conclusion The HACE model can be established effectively by simulating conditions at the altitude of 6000 m(the atmospheric pressure being 47.19 kPa and the oxygen partial pressure being 9.73 kPa)with a HH chamber.关键词
高原反应/高原脑水肿/血脑屏障/低压低氧Key words
Altitude sickness/High-altitude cerebral edema/Blood-brain barrier/Hypobaric hypoxia引用本文复制引用
春花,白玛康卓..高原脑水肿小鼠模型的建立与鉴定[J].四川大学学报（医学版）,2023,54(6):1269-1275,7.基金项目
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)和西藏自治区科技厅重点研发与转化项目(No.XZ202101ZY0009G)资助 （No.zdbs202213）
