X线全脑照射对小鼠脑微血管及血脑屏障的影响  

Influence of whole-brain irradiation by X-ray in capillaries and blood-brain barrier in mouse brains

作　　者：邓哲治 黄海威[1] 吴萌萌[1] 何国永[1] 

机构地区：[1]中山大学附属第一医院神经科,广州510080

出　　处：《中华神经医学杂志》2015年第5期454-459,共6页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（81271386）

摘　　要：目的 探讨放射性脑损伤中可能存在的脑微血管损伤及血脑屏障破坏情况.方法 70只8周龄雄性BALB/C小鼠应用随机数字表分为照射组和对照组,其中照射组行X线全脑照射（单次10 Gy剂量）.分别在照射后1、7、30、90、180 d取材（每组每个观察点7只小鼠）,采用HE染色观察脑组织微血管形态的改变,采用免疫荧光染色检测全脑第Ⅷ因子相关抗原（vWF）及ZO1蛋白的表达变化.结果 照射后1d开始,照射组小鼠即可见微血管有扩张紊乱,血管内皮细胞与基膜分离,但血管壁仍较薄,血管周隙正常;照射后7d出现血管壁增厚、管腔狭窄;照射后30 d管腔狭窄逐渐加重甚至闭塞,部分血管可见血栓形成,血管周隙开始增大,并持续至180d.与对照组比较,照射后各时间点照射组小鼠脑组织vWF、ZO1蛋白表达阳性细胞数明显减少（vWF：1 d：23.17±2.93 vs 15.80±2.39,7 d：21.25±2.33 vs 11.60±2.30,30 d：19.78±2.16vs 8.20±1.64,90 d：17.21±3.31 vs6.00±2.12,180 d：16.98±1.92 vs 3.80±2.59;ZO1：1 d：26.17±3.31 vs 15.40±1.82,7 d：23.20±2.93vs12.00±1.58,30 d：20.88±2.20vs 9.10±2.55,90 d：18.32±1.87 vs 6.20±1.92,180 d：17.50±1.91vs 2.40±1.52）,差异均有统计学意义（P＜0.05）;且随着时间延长,照射组小鼠脑组织vWF、ZO1蛋白阳性表达细胞数亦逐渐减少,各时间点间比较差异亦均有统计学意义（P＜0.05）.结论 X线全脑照射能诱导小鼠脑微血管持续损伤及血脑屏障紧密连接破坏,导致放射性脑损伤的发生发展.Objective To investigate the possible presence of radiation brain injury （RBI） in vascular injury and blood-brain barrier （BBB） damage.Methods Seventy 8 weeks old male BALB/C mice were randomly divided into irradiation group and control group;mice in the two groups received whole-brain exposure with a single dose of 10 Gy irradiation or sham irradiation.Tissue samples were taken 1,7,30,90 and 180 days after irradiation （7 mice in each time point per group）;HE staining was used to observe the microvascular morphology and density changes;immune-fluorescence staining was used to visualize the differential expressions of factor Ⅷ related antigen （vWF） and zonulaoccludens-1 （ZO-1）.Results Micro-vascular disorders began to appear from the first day of irradiation,deteriorating with time extension gradually.After the X-ray irradiation exposure,the protein expressions of vWF and ZO-1 in the irradiation group were significantly decreased as compared with those in the control group 1,7,30,90 and 180 days after irradiation （vWF：23.17±2.93 vs 15.80±2.39,21.25±2.33 vs 11.60±2.3,19.78±2.16 vs 8.20±1.64,17.21±3.31 vs 6.00±2.12 and 16.98±1.92 vs 3.80±2.59;ZO1：26.17±3.31 vs 15.40±1.82,23.20±2.93 vs 12.00±1.58,20.88±2.20 vs 9.10±2.55,18.32±1.87 vs 6.20±1.92 and 17.50±1.91 vs 2.40±1.52,P〈0.05）;besides,the decreased expression ofvWF and ZO-1 in the irradiation group showed a time-depended manner,with significant differences between each two time points （P〈0.05）.Conclusion X-rays may induce persistent micro-vascular injury and destroyed BBB tight junctions,which may be closely related to the occurrence and development of RBI.

关 键 词：X线照射 放射性脑损伤 微血管 血脑屏障 

分 类 号：R818[医药卫生—放射医学]