丁苯酞对放射性脑损伤大鼠血脑屏障的影响  

Effects of 1-3-n-Butylphthalide on the blood-brain barrier following whole brain irradiation in rats

作　　者：陈应柱 张娴娴 肖璐 戚艳红 杨璞 田野[2] 包仕尧[2] 

机构地区：[1]扬州大学临床医学院神经科,225001 [2]苏州大学附属第二医院放疗科

出　　处：《中华放射肿瘤学杂志》2012年第4期392-395,共4页Chinese Journal of Radiation Oncology

基　　金：江苏省卫生厅重大科研课题（K200406）

摘　　要：目的观察大鼠单次全脑照射后血脑屏障改变和丁苯酞的干预作用，探讨其对放射性脑损伤的防护作用机制。方法144只SD大鼠随机分为空白对照组、单纯照射组、单纯丁苯酞组、丁苯酞联合照射组。照射采用4MVX线单次10Gy全脑照射，丁苯酞分别按0．3、1．0、3．0mg／kg腹腔注射。测定脑组织依文思蓝（EB）含量，免疫组化法分析脑组织血管内皮生长因子（VEGF）表达，心脏取血计数循环内皮细胞（CEC）数，用MRI观察T1、T2加权信号强度以及信号强度增强率。组问比较采用方差分析中的Student—Newman—Keuls检验。结果与空白对照组比较，单纯照射组大鼠脑组织EB含量、VEGF表达、CEC数明显增高[2．81：7．82（P=0．002）、5．83：10．26（P=0．003）、3．16：6．1d（P=0．002）]，T1加权信号强度降低（P=0．004—0．018），T2加权信号强度及信号强度增强率升高（P=0．007～0．036）。与单纯照射组比较，丁苯酞联合照射组大鼠脑组织EB含量、VEGF表达、CEC数均降低[7．80：3．86（P=0．007）、10．83：5．26（P=0．008）、6．36：3．64（P=0．009）]，T1、T2加权信号强度及信号强度增强率改变均降低（P=0．008～0．026、0．006—0．038）。结论丁苯酞通过降低大鼠全脑照射后脑组织VEGF表达、CEC数来降低血脑屏障通透性。Objective To investigate the effects of 1-3-n-Butylphthalide on the blood-brain barrier （BBB） following whole brain irradiation in rats. Methods 144 male Sprague Dawley rats were randomly divided into sham-irradiation group, irradiation group, 1-3-n-Butylphthalide group, and irradiation plus 1-3- n-Butylphthalide group. Whole-brain irradiation was given as a single-dose of 10 Gy using 4 MV X-ray. The rats were injected intraperitoneally with 1-3-n-Butylphthalide at 0. 3 mg/kg, 1.0 mg/kg, 3.0 mg/kg once per day. The changes of the BBB were assessed by Evans blue （EB） assay. The expression of vascular endothelial growth factor （VEGF） in the brain tissue was determined by immunohistochemistry. The circulating endothelial cells （CECs） isolated from right ventricular blood were counted. MRI was evaluated with the T1-weighted images, T2-weighted images and MRI enhancement images induced by Gd-DTPA. The data were compared among the groups through Student-Newman-Keuls test. Results Compared with the sham-irradiation group, the EB content, the expression of VEGF in the brain tissue and the CECs were significantly increased in the irradiation group （2. 81： 7. 82, P = 0. 002;5.83： 10. 26, P = 0. 003;3.16： 6. 14, P = 0. 002）. The signal intensity of T1-weighted images was significantly decreased while T2-weighted images and the enhancement rate significantly increased in the irradiation group （P= 0. 004 -0.018）. Compared with irradiation group, the EB content, the expression of VEGF and the CECs were decreased significantly in the irradiation plus 1-3-n-Butylphthalide group （ 7.80： 3.86, P = 0. 007 ; 10. 83 ： 5.26, P = 0. 008 ;6.36： 3.64, P = 0. 009）. However, the changes in the MRI were significantly attenuated （ P = 0. 008 - 0. 026, and O. 006 - O. 038, respectively ）. Conclusions Following whole brain irradiation, 1-3-n- Butylphthalide can decrease the permeability of the BBB in rats via decreasing VEGF expression and decreasing the CECs.

关 键 词：血脑屏障 辐射防护 丁苯酞 

分 类 号：R818[医药卫生—放射医学] R965[医药卫生—临床医学]