大鼠放射性脑损伤所致血脑屏障通透性改变与EBA及VEGF表达的相关性研究

A correlation study of blood-brain barrier permeability changes and EBA, VEGF expression in rats following radiation-induced brain injury

目的探究脑皮质内皮屏障抗原(EBA)及血管内皮生长因子(VEGF)在放射性血脑屏障损害条件下的动态变化规律,为临床提供参考。方法使用随机数字表法将48只清洁级雄性SD大鼠分为对照组和放射性脑损伤后7、14和28 d 4组,每组12只。采用X线电子计算机断层扫描设备制备大鼠放射性脑损伤模型。大鼠按照3 m L/kg的剂量尾静脉注射3%伊文思蓝(EB),开颅并暴露脑皮质血管,放于微循环显微镜下观察EB渗出情况,并借助微循环显微成像系统评估血脑屏障通透性;使用免疫组化染色的方法来检测各组大鼠脑皮质EBA和VEGF的表达。结果与对照组相比,损伤组大鼠脑皮质微血管EB外渗量和VEGF的表达水平于伤后7、14、28 d均有不同程度升高(均P<0.05),从伤后7 d至28 d逐渐降低,损伤各亚组之间差异均有统计学意义(均P<0.05),二者呈正相关(r=0.898,P<0.001);EBA表达水平于伤后各个时间点均下降(均P<0.05),从伤后7 d至28 d逐渐升高,损伤各亚组之间差异均有统计学意义(均P<0.05),与EB外渗量呈负相关(r=-0.866,P<0.001)。结论大鼠放射性脑损伤后血脑屏障通透性增加与EBA表达减少、VEGF表达增加具有重要关联性。

Objective To explore the dynamic changes of endothelial barrier antigen (EBA) and vascular endothelial growth factor (VEGF) expressions in cerebral cortex under the condition of blood-brain barrier damage in rats following radi?ation-induced brain injury, which provided clinical references. Methods Forty-eight clean grade male SD rats were divid?ed into the control group and 7 d, 14 d, 28 d after brain irradiation group (n=12 for each group) by using stochastic indicator method. The radiation-induced brain injury model was established by using electronic computer X-ray tomography tech?nique. The 3%Evans blue (EB) was injected into rats according to the dose of 3 mL/kg via the tail vein, then the blood ves?sels of cerebral cortex were exposed after having a craniotomy. EB extravasation was detected by microcirculation micro?scope. The permeability of blood-brain barrier was evaluated by using microscope vascular camera device. The expressions of EBA and VEGF in the cerebral cortex were measured by immunohistochemistry staining in each group. Results Both of EB extravasation and VEGF expression in rat cerebral cortex were significantly increased in injury group at day 7, 14 and 28 after brain irradiation compared with those of control group (P<0.05), and which were gradually decreased from day 7 to day 28 after brain irradiation. There were significant differences in EB extravasation and VEGF expression between the injury subgroups (P<0.05). There was a positive correlation between EB extravasation and VEGF expression (r=0.898, P<0.001). The expression levels of EBA were decreased at different time points in injury groups compared with those of control group (P<0.05), and gradually increased from day 7 to 28 after injury. There were significant differences in expression levels of EBA between injury subgroups (P<0.05). The expression of EBA was negatively correlated with EB extravasation (r=-0.866, P<0.001). Conclusion The increases of blood-brain barrier permeability have important relation to the decreases of EBA expression and the increases of VEGF expression after radiation-induced brain injury.