白介素-1β增加血脑肿瘤屏障通透性的作用机制

发布时间：2018-02-02 11:06

本文关键词： 血管内皮生长因子白介素-β 血肿瘤屏障 caveo-lin- 胶质瘤质膜微囊小凹　出处：《中国药理学通报》2016年01期 　论文类型：期刊论文

【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。
[Abstract]:Objective to study interleukin-1 尾 interleukin-1 尾. IL-1 尾 was used to treat vascular endothelial growth factor (VEGF) in glioma cells. The expression of plasma membrane microcapsule structural protein (caveolin-1) in cerebrovascular endothelial cells and the effect of plasma membrane microcapsule fovea. To explore the possible mechanism of IL-1 尾 opening blood tumor barrier. Methods the model of blood tumor barrier in vitro was established by Transwell. VEGF in glioma cells was dynamically monitored by IL-1 尾 by blot. The expression of caveolin-1 protein in cerebrovascular endothelial cells was observed by transmission electron microscope. The effect of IL-1 尾 on blood tumor barrier permeability was evaluated by fluorescein sodium exudation test. Results the blood tumor barrier model in vitro was successfully established. When IL-1 尾 acted on the blood tumor barrier model in vitro. The expression of VEGF protein increased and reached its peak at 60min. The blood tumor barrier permeability in vitro was also maximum at 60min after exposure to IL-1 尾. The model of blood-tumor barrier was treated with IL-1 尾 for 60min. The expression level of plasma membrane microcapsule structure protein (caveolin-1) and the number of plasma membrane microcapsule fovea reached the peak in the cerebral microvascular endothelial cells, and then decreased. Conclusion IL-1 尾 can increase the permeability of blood tumor barrier. This effect may be related to the increase of the number of microvesicles in plasma membrane by IL-1 尾 via VEGF/caveolin-1 pathway.
【作者单位】：华北理工大学基础医学院;
【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)
【分类号】：R322.81
【正文快照】： 神经胶质瘤简称胶质瘤,是起源于神经胶质细胞的一种恶性脑肿瘤。目前临床上对神经胶质瘤的治疗大多主张综合治疗,即临床手术后配合放化疗等,以此来延长患者的生存时间,遏制其复发[1-2]。在临床胶质瘤的治疗过程中,由于血肿瘤屏障的存在,化疗药物无法直接进入病灶,即使有少量进

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