首页> 中文期刊> 《中国药理学通报》 >白介素-1β增加血脑肿瘤屏障通透性的作用机制

白介素-1β增加血脑肿瘤屏障通透性的作用机制

             

摘要

Aim To study the effect of IL-1β on pro-tein expression of vascular endothelial growth factor in glioma cells and plasma membrane microcapsule struc-ture protein caveolin-1 and plasma membrane vesicles in brain microvascular endothelial cells, and prelimi-narity discuss the possible mechanism of IL-1β opening blood tumor barrier. Methods The tumor barrier mod-el 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 fluores-cein 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 60min,and recovered to the initial state at 120min. The permeability of the blood tumor barrier model was the highest at 60min. In addition,our re-sults also found that,the protein expression of plasma membrane microcapsule structure protein caveolin-1 and number of plasma membrane vesicles in brain mi-crocapsule endothelial cells reached peak at 60 min, subsequently reduced and returned to non drug state at 120min. Conclusion IL-1β increases blood tumor barrier permeability,which may be related to IL-1β in-creasing the number of plasma membrane vesicles through VEGF/ caveolin-1 pathway.%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。

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