白介素-1β在缓激肽开放血脑屏障过程中的作用及其机制

Effect and mechanism of interleukin-1β in process of opening the blood-brain barrier by bradykinin

目的探讨白介素-1β(IL-1β)在缓激肽(BK)开放血脑屏障(BBB)过程中的作用及其机制。方法缓激肽处理C6细胞后,动态观察培养液中IL-1β含量(放射免疫法)、C6细胞内热休克因子1(HSF1)蛋白的表达(Western blot法)及IL-1β的mRNA水平(RT-PCR法)。利用伊文思蓝检测C6恶性胶质瘤大鼠经颈内动脉给予IL-1β及缓激肽后血脑屏障的通透性。结果缓激肽作用于C6细胞后,培养液中IL-1β的含量明显增加,于120 min含量最多,其后开始减少。C6细胞内HSF1的表达及IL-1β的mRNA水平也在给予缓激肽后明显增加,并分别于干预后的30 min和60 min达高峰后逐渐减少。缓激肽与IL-1β单独作用于C6动物后均可引起胶质瘤大鼠的血脑屏障通透性增加,且IL-1β对肿瘤模型动物血脑屏障通透性的影响与C6细胞培养液中IL-1β的含量相一致。结论 IL-1β可能介导了缓激肽开放血脑屏障的作用,此作用可能是由于缓激肽诱导C6细胞内HSF1的表达增加,增加的HSF1促进神经胶质瘤细胞释放IL-1β所致。

Aim To investigate the effects of interleukin-1β（IL-1β） in process of opening blood-brain barrier（BBB） by bradykinin（BK） and its mechanism.Methods Contents of IL-1β in nutrient fluid（radioimmunity method）,HSF1 protein expression（by Western blot） and levels of IL-1β the mRNA（by RT-PCR method） for C6 cells were dynamically observed,after BK treatment.Using Evans blue was applied to detect permeability of BBB after intracarotid infusion of IL-1β for C6 rats.Results For C6 cells,contents of IL-1β in the nutrient fluid were obviously increased after BK treatment and achieved the peak at 120 min,also BK significantly increased expressions of HSF1 and levels of IL-1β mRNA in C6 cells and reached the peak at 30 min and 60 min,separately.Permeability of BBB of C6 animals was in conformity with concentrations of IL-1β in nutrient fluid after BK treatment.Conclusion The IL-1β may mediate the effects of opening the BBB by bradykinin,which may be related with increased HSF1 expression caused by BK and the increased HSF1 promoted neurospongioma cell to release IL-1β.