脑出血后血红蛋白对血脑屏障的影响  

Effect of hemoglobin on blood-brain barrier in rat models after intracerebral hemorrhage

作　　者：杨硕[1] 陈祎招[1] 邓心情[1] 蒋伟平[1] 李兵[1] 付正浩[1] 柯以铨[1] 

机构地区：[1]南方医科大学珠江医院神经外科,广东神经外科研究所,广东省脑功能修复与再生重点实验室,广州510282

出　　处：《中华神经医学杂志》2013年第4期364-368,共5页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（81271314、30500526）;广东省自然科学基金（5300468）;广东省教育部产学研结合项目（20128091100154）;国家临床重点建设专科资助项目

摘　　要：目的探讨脑出血后血红蛋白（fro）对血脑屏障结构和功能的影响。方法108只雄性SD大鼠按随机数字表法分为正常对照组（12只）、Hb组（48只）和假手术组（48只）；再进一步依据模型制作完成后观察时间点的不同，将Hb组和假手术组分为6h、24h、3d、7d共4个亚组（每个亚组12只1。应用HE染色、铁染色分别观察Hb注入大鼠脑内后组织学变化和铁离子释放规律。利用伊文氏蓝检测血脑屏障的通透性。免疫荧光和荧光定量PCR检测血脑屏障紧密连接蛋白claudin-5和ZO．1表达的变化。结果Hb注入后大鼠脑组织中可见明显的水肿坏死，3d和7d时可见铁离子的释放和蓄积。Hb组的伊文氏蓝渗出量明显高于假手术组，差异有统计学意义（P〈0．05）。免疫荧光结果显示Hb注入大鼠脑内后可见血管内皮细胞间紧密连接蛋白claudin．5和ZO-1表达不连续，表达水平下降。在mRNA水平，Hb组claudin．5和ZO-1表达水平明显低于假手术组，差异有统计学意义f氏0．05）。结论脑出血发生后，Hb可能直接引起血脑屏障结构和功能的破坏．进而参与脑水肿的发生、发展过程。Objective To investigate the effect of hemoglobin on structure and function of blood-brain barrier （BBB） in rat models after intracerebral hemorrhage. Methods One hundred and eight male SD rats were randomized into normal control group （n= 12）, intracerebral hemoglobin injection group （Hb group, n=48） and sham-operated group （n=48）; according to the different observation time points, rats in the Hb group and sham-operated group were divided into 4 subgroups （6 and 24 h, 3 and 7 d after the injection, n=12）. Histological changes and iron deposition of the brain tissues were examined with HE staining and iron staining, respectively. BBB permeability was evaluated by the permeation of Evens blue. The expressions of claudin-5 and ZO-1 in perihematomal brain tissues were detected by immunoftuorescence staining and real-time fluorescence quantitative PCR. Results Evident edema and necrosis were observed in the perihematomal zone of lib group, and iron deposition was found 3 and 7 days after the injection. The permeation of Evens blue in Hb group was significantly increased as compared with that in sham-operated group （P〈0.05）. Immunofluorescence staining indicated that expressions of claudin-5 and ZO-1 were low and discontinuous in Hb group; the mRNA expression levels of claudin-5 and ZO-1 in Hb group were significantly lower than those in the sham-operated group （P〈 0.05）. Conclusion After intracerebral hemorrhage, Hb may induce the damage of BBB and participate in the course of brain edema.

关 键 词：血红蛋白 血脑屏障 紧密连接 脑水肿 

分 类 号：R285.5[医药卫生—中药学]