低O2高CO2对小鼠血脑屏障及水通道蛋白-4表达的影响

目的：探讨低O2高CO2对小鼠血脑屏障通透性、超微结构及水通道蛋白-4（AQP4）表达的影响。方法：雄性成年C57BL/6小鼠,随机分为对照组（C组）、实验组（低O2高CO21d、2d、3d、1周、2周组）,实验组动物置于低O2高CO2舱造模。小鼠腹腔注射荧光素钠,观察不同时间点血脑屏障通透性的变化,电镜观察血脑屏障超微结构的变化,免疫组化及RT-PCR分别检测小鼠前额叶皮层及海马AQP4蛋白及mRNA表达的变化。结果：实验1d组小鼠血脑屏障的通透性升高最明显,然后逐渐下降,在1周内仍显著高于对照组（P〈0.05或P〈0.01）,2周末回落至对照组水平（P〉0.05）。实验1d组小鼠血脑屏障超微结构有明显改变,皮层及海马脑组织AQP4蛋白及mRNA表达显著增高（P〈0.05）。结论：低O2高CO2在早期能使小鼠血脑屏障的通透性升高,可能与AQP4的表达增高有关。

Hypoxic hypercapnia increased blood-brain barrie's permeability and expression of AQP4 in mice

Objective： To investigate the changes of the permeability and ultrastructure of mice＇s blood-brain barrier （BBB） and expression of aquaporin-4 （AQP4） caused by hypoxic hypercapnia. Methods： The male adult C57BL/6 mice were randomly divided into six groups： the control group （C）, the hypoxic hypercapnia 1 d, 2 d, 3 d, 1 w and 2 w group. Experimental mice were exposed to normobaric hypoxic hypercapnia by placing them in a chamber. Sodium fluorescein （NaFI） was injected intraperitoneally to detect the permeability of BBB. The BBB ultrastructure was observed by electron microscope. The expression of AQP4 mRNA and protein levels were measured by Immunochemistry and PT-PCR. Results： Compared with C group, the permeability of mice＇s BBB increased significantly in 1 d, 2 d, 3 d and 1 w group （P〈0.05 or P〈0.01）, which declined gradually with the prolongation of hypoxic hypercapnic exposure andhad no significant increase in 2 w group. BBB ultrastructure changes were observed by electron microscope and mRNA and protein of AQP4 were upregulated significantly in 1 d group （P〈0.05）. Conclusion： The blood-brain barrier＇s permeability may increase with miee＇s exposure to hypoxic hypercapnia at early stage, which may have the relationship to the upregulaion of AQP4.