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目的探讨血肿周边脑组织中HIF-1α蛋白的表达变化与血脑屏障(BBB)通透性之间的关系。方法SD大鼠56只随机分假手术对照组(sham组)和脑出血组(ICH组)。ICH组又分为6h组、24h组、3d组、7d组和14d组,每组8只。采用自体血脑内注射法建立脑出血动物模型,测定血肿周边脑组织中伊文思蓝(EB)外渗量,以EB外渗量反映BBB通透性的变化,以免疫组化方法检测脑出血后不同时间血肿周边脑组织中HIF-1α蛋白表达情况,并应用干湿比重法测定脑组织含水量。结果脑出血后3d内,BBB通透性和脑组织含水量均呈进行性增加,并于出血后第3d达到高峰,此后逐渐下降,对照组与出血组脑组织含水量及BBB通透性比较差异均有统计学意义(P<0.05);脑出血组HIF-1α蛋白阳性表达率60.42%(29/48),对照组HIF-1α蛋白阳性表达率为0%,二者相比差异有统计学意义(P<0.05);脑出血后,HIF-1α蛋白表达于出血后3d达到高峰并维持到第7d,脑出血后不同时间阳性率比较差异有统计学意义(P<0.05)。HIF-1α的表达变化与BBB通透性和脑组织含水量均呈正相关(P<0.05)。结论HIF-1α在血肿周边脑组织中的表达与BBB通透性改变及脑水肿的形成和发展密切相关。
Objective To investigate the relationship between the expression of HIF-1α protein and the permeability of blood-brain barrier (BBB) in perihematomal brain tissue. Methods Fifty-six SD rats were randomly divided into sham operation group (sham group) and ICH group (ICH group). ICH group was divided into 6h group, 24h group, 3d group, 7d group and 14d group, 8 rats in each group. The animal model of intracerebral hemorrhage was established by autologous intracerebral injection. The extravasation of Evans blue (EB) in the brain tissue around the hematoma was measured. The EB extravasation was used to detect the changes of permeability of the BBB. The cerebral hemorrhage was detected by immunohistochemistry HIF-1αprotein expression in the perihematomal brain tissue at different time points was measured, and the water content of brain tissue was measured by the wet-dry proportion method. Results Within 3 days after intracerebral hemorrhage, BBB permeability and brain water content increased progressively and peaked on the third day after hemorrhage, and then decreased gradually. The water content and BBB permeability of the control group and hemorrhage group were compared (P <0.05). The positive expression rate of HIF-1α protein in cerebral hemorrhage group was 60.42% (29/48), while the positive expression rate of HIF-1α protein in control group was 0%, the difference was statistically significant (P <0.05). After intracerebral hemorrhage, the expression of HIF-1αprotein peaked at 3d on the 7th day after hemorrhage, and there was significant difference at different time after cerebral hemorrhage (P <0.05). The expression of HIF-1α was positively correlated with the permeability of BBB and the water content of brain tissue (P <0.05). Conclusion The expression of HIF-1α in the perihematomal brain tissue is closely related to the change of BBB permeability and the formation and development of cerebral edema.