低压低氧大鼠脱适应期血脑屏障通透性和脑微血管密度的变化

Changes of brain microvessel density and BBB permeability in rats experimentally induced hypobaric hypoxia to normoxia

目的探讨实验性低压低氧大鼠在脱适应期血脑屏障(BBB)通透性和脑微血管密度(MVD)的变化。方法雄性SD大鼠72只随机分为低压低氧模型组和对照组,将模型组大鼠置于模拟海拔4 000 m的高原环境模拟舱内,氧浓度12. 6%,连续暴露4周后让其重返常氧环境,按照返回常氧环境不同时间点再随机分成5个亚组(n=12,重返常氧环境后第1,3,7,14,30天),分别检测BBB通透性和脑MVD,BBB检测采用伊文氏蓝(EB)示踪法结合脑组织EB含量测定,MVD采用免疫组化法检测脑组织CD34+细胞的表达。结果与对照组相比,低压低氧模型组大鼠脑组织EB含量明显增加(P <0. 01),随着返回常氧环境时间的延长而逐渐呈降低的趋势,与返回常氧环境时间呈显著负相关(r=-0. 898,P=0. 038);与BBB通透性变化一致,模型组大鼠脑组织CD34+细胞数明显增多(P <0. 01),与返回常氧环境时间呈显著负相关(r=-0. 883,P=0. 016)。结论低压低氧大鼠在脱适应期BBB通透性和脑MVD发生了明显的变化,高原脱适应反应的发生可能与其改变有关。

Objective To investigate the blood-brain barrier( BBB) permeability and brain microvessel density( MVD) changes in the plateau de-adaptation period. Methods Seventy-two clean and healthy adult male SD rats were randomly assigned into hypobaric hypoxia model group and control group. All rats in model group were continuously kept in the simulated four kilometers plateau environment for four weeks,then were randomly divided into five sub-groups( n = 12) according to different time( 1,3,7,14,30 d) after the rats returned to the normal oxygen environment. BBB permeability and MVD were detected. Results Compared with control group,the EB contents in model group were significantly increased( P < 0. 01),which were gradually decreased with time. The EB content was negatively correlated with the time of returning to the normal oxygen environment( r =-0. 898,P = 0. 038). CD34^+ cell number was significantly more in model group than in control group( P < 0. 01),and it was negatively correlated with the time of returning to the normal oxygen environment( r =-0. 883,P = 0. 016). Conclusion These results show that there were significant changes in brain MVD and BBB permeability of rats from experimentally induced hypobaric hypoxia to normoxia,which might be caused by the plateau de-adaptive response.