| Objectives:The expression of HIF-1α,AQP4 and tight junctions（Claudin-5、Occludin、ZO-1）and morphological changes in rat brain tissue were studied under acute hypobaric hypoxia.It will be to investigate the effects of acute hypobaric hypoxia on blood-brain barrier-associated junctional proteins and permeability in rats.Methods:48 male SD rats were randomly divided into four groups:control group and 7000 m hypobaric hypoxia group for 24 h,48 h and 72 h.Each hypoxic group was treated by continuous hypoxia in a hypobaric chamber at a simulated altitude of 7000 m（305 mm Hg,PO2 63.7 mm Hg）.The changes of mental state,body weight,brain water content（dry and wet weight method）and blood-brain barrier permeability（evans blue method）were observed,the expression of HIF-1α,AQP4,Claudin-5,Occludin and ZO-1 m RNA in rat brain tissue were detected by q RT-PCR,the expression levels of AQP4、Occludin and ZO-1 protein in rat brain tissue were evaluated by Western blot.To explore the effect of acute hypobaric hypoxia on the blood-brain barrier and the impact of permeability,combined with the changes in brain tissue morphology in rats.Results:（1）After entering the low-pressure chamber（7000 m）,the rats showed reduced mobility,reduced eating and drinking,and gradually erected back hairs and weight loss.（2）Evens blue staining results showed that the blood-brain barrier permeability of rats in the 7000 m hypobaric hypoxia 24 h group was increased（p<0.05）.（3）There was no significant difference in the expression of AQP4 m RNA in the rat brain tissue in each group.The expression of Claudin-5 m RNA of tight junctions in the 7000 m hypobaric hypoxia 48 h group increased significantly（p<0.05）.The expression of Occludin and ZO-1 m RNA of tight junctions in the 7000m hypobaric hypoxia 48 h group and 72 h group increased significantly（p<0.05）.The expression of HIF-1αm RNA increased gradually with the increase of hypoxia time.（4）The expression levels of AQP4 and Occludin protein in rat brain tissue were increased significantly in the 7000 m hypobaric hypoxia 72 h group（p<0.05）,and the expression levels of ZO-1 protein was increased significantly in the 7000 m hypobaric hypoxia 48 h group（p<0.05）.（5）The morphological observation of brain tissue showed that the morphology of neurons was changed in all groups of hypobaric hypoxia,simulating 7000 m hypoxia for different times.It manifested varying degrees as deep staining of nuclei,enlarged intercellular and perivascular spaces.Compared with the control group,the morphological changes of the hypobaric hypoxia 24 h group were not significant.The hypobaric hypoxia 48 h group occasionally saw cell vacuolation,and the hypobaric hypoxia 72 h group rat brain tissue cells had increased vacuolation,edema,and glial cell proliferation.Conclusion:The increased expression of HIF-1αin brain tissue under acute hypobaric hypoxia may have affected the permeability of the BBB by affecting the expression of AQP4,Claudin-5,Occludin and ZO-1,causing alterations in the function and structure of the BBB,and these changes may be involved in the occurrence and development process of HACE. |
