放射性脑损伤大鼠早期血脑屏障的改变

目的研究大鼠受到全脑照射后早期血脑屏障(BBB)的改变。方法建立清醒状态下大鼠放射性脑损伤模型,采用4MeV电子线作30Gy的单次全脑照射。120只SD大鼠随机分为照射组和假照射组,分别于照射前即刻、照射后6h、1d、1周和1月时记录磁共振成像(MRI)T1加权、T2加权的信号强度及其增强率,测定脑组织中伊文思蓝(EB)含量,免疫组化分析海马区神经细胞血管内皮生长因子(VEGF)的表达,并观察病理形态学的改变。结果照射组照射后T1加权的信号强度降低,T2加权的信号强度和信号强度的增强率升高,脑组织EB含量在照射后6h、1周和1月时及照射后6h VEGF表达较假照射组升高(P<0.05或0.01)。结论放射性脑损伤后早期,VEGF表达上调,BBB通透性增加,导致早期放射性脑损伤的发生。

The Study on Changes of the Blood-brain Barrier after Radiation-induced Brain Injury in the Early Stage in Rats

Objective To investigate the changes of the blood-brain barrier(BBB) after radiation-induced brain injury in the early stage.Methods One hundred and twenty healthy male SD rats weighing 240~270g were ran-domly divided into 2 group with 30 rats in each group:radiation and sham radiation group.The rats were placed in a prone position awake without any anesthetics.The whole brain was irradiated by 4 MeV electron beam at a single dose of 30 Gy.The changes in BBB were assessed by(1) magnetic resonance imaging(MRI) with the T1-weighted images,T2-weighted images and MRI enhancement images induced by Gd-DTPA;(2) Evans blue(EB) assay;2% EB 3 mL.kg-1 was injected via femoral vein and 3h later the animals were decapitated and the content of EB in the brain tissue was determined by spectrophotometry;(3) The expression of vascular endothelial growth factor(VEGF) in the brain tissue determined by immuno-histochemistry before irradiation(T0)(baseline) at 6h(T1),1 day(T2),1 week(T3)and 1 month(T4)after irradiation.Results In radiation group,the signal intensity of T1-weighted images significantly decreased while the signal intensity of T2-weighted images and the enhancement rate signifi-cantly increased at T4.The content of EB at T1-T4 and the expression of VEGF at T1,T2,T4 were significantly higher in radiation group than in sham radiation group.Conclusion The brain edema of rats and the injury of BBB became more and more severe gradually after irradiation.The results indicated that VEGF played an important role in the brain radiation injury in the early stage by the increasing of the BBB permeability and the edema of brain tissue.