白介素-1β增加血脑肿瘤屏障通透性的作用机制  

Mechanism of IL-1β enhance Blood-Brain Tumor Barrier permeability

作　　者：王健 孙月明 秦丽娟 

机构地区：[1]华北理工大学基础医学院,河北唐山063000

出　　处：《中国药理学通报》2016年第1期94-97,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81101912);河北省中医药管理局中医药类科研项目(No 2014195);河北省卫生厅科学研究基金项目(No 20150491);河北省科技计划项目(No 152777189)

摘　　要：目的研究白介素-1β(interleukin-1β,IL-1β)对胶质瘤细胞内血管内皮生长因子(vascular endothelial growth factor,VEGF)、脑血管内皮细胞内质膜微囊结构蛋白caveolin-1表达和质膜微囊小凹的影响,初步探讨IL-1β开放血肿瘤屏障的可能机制。方法利用Transwell制备体外血肿瘤屏障模型。Western blot法动态监测IL-1β对胶质瘤细胞内VEGF、脑血管内皮细胞内caveolin-1蛋白表达水平的影响。透射电镜观察脑血管内皮细胞内质膜微囊小凹的数量,荧光素钠渗出实验评估IL-1β对血肿瘤屏障通透性的影响。结果成功建立了体外血肿瘤屏障模型。当IL-1β作用于体外血肿瘤屏障模型后,VEGF蛋白的表达量增加,于60min时达到峰值,至120min时恢复到初始状态。体外血肿瘤屏障通透性亦于IL-1β作用60min时最大。另外,我们的研究结果还发现,IL-1β作用于血肿瘤屏障模型60min时,脑微血管内皮细胞中质膜微囊结构蛋白caveolin-1的蛋白表达水平及质膜微囊小凹的数量达到峰值,其后减少,并于120min时恢复到未给药状态。结论 IL-1β增加了血肿瘤屏障的通透性,此作用可能与IL-1β通过VEGF/caveolin-1途径增加了质膜微囊小凹数量有关。Aim To study the effect of IL-1β on protein expression of vascular endothelial growth factor in glioma cells and plasma membrane microcapsule structure protein caveolin-1 and plasma membrane vesicles in brain microvascular endothelial cells,and preliminarity discuss the possible mechanism of IL-1β opening blood tumor barrier. Methods The tumor barrier model was established by transwell in vitro. The effect of IL-1β on the expression of VEGF in glioma cells and caveolin-1 in brain microvascular endothelial cells was dynamically monitored by Western blot. TEM was used to observe the number of plasma membrane vesicles of brain microvascular endothelial cells. Sodium fluorescein leakage test was used to assess the permeability of blood tumor barrier after IL-1β. Results The tumor barrier model was successfully established by transwell in vitro. When IL-1β treated the model of blood tumor barrier,the expression of VEGF increased,and reached the peak at 60 min,and recovered to the initial state at120 min. The permeability of the blood tumor barrier model was the highest at 60 min. In addition,our results also found that,the protein expression of plasma membrane microcapsule structure protein caveolin-1and number of plasma membrane vesicles in brain microcapsule endothelial cells reached peak at 60 min,subsequently reduced and returned to non drug state at120 min. Conclusion IL-1β increases blood tumor barrier permeability,which may be related to IL-1β increasing the number of plasma membrane vesicles through VEGF / caveolin-1 pathway.

关 键 词：血管内皮生长因子 白介素-1Β 血肿瘤屏障 caveo-lin-1 胶质瘤 质膜微囊小凹 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]