罂粟碱与缓激肽配伍开放血肿瘤屏障机制的初探  

Elementary inquiry into the mechanism of annexation of bradykinin and papaverine on BTB opening

作　　者：乔文芳[1] 刘坤[1] 薛一雪[1] 

机构地区：[1]中国医科大学基础医学院神经生物学教研室,辽宁沈阳110001

出　　处：《中国药理学通报》2008年第11期1436-1440,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30670723;30570650;30600060);辽宁省自然科学基金资助项目(No20052102);沈阳科学技术计划资助项目(No1072033-1-00)

摘　　要：目的探讨罂粟碱与缓激肽配伍对血肿瘤屏障开放是否有协同效应,以及细胞因子IL-1β在血肿瘤屏障开放机制中的作用。方法♀Wistar大鼠160只,随机分为8组,即假手术组,模型组,罂粟碱(PA)组,缓激肽(BK)组,PA+BK组,1/2PA+BK组,1/2BK+PA组,1/2PA+1/2BK组。每组20只。建立大鼠C6胶质瘤模型,颈内动脉给药,通过电镜观察紧密连接开放程度,用伊文斯蓝检测血肿瘤屏障通透性。应用Western法测定各组大鼠肿瘤组织内白细胞介素-1β(IL-1β)蛋白表达的变化。应用免疫组织化学法测定各组大鼠肿瘤部位脑微血管周围IL-1β蛋白表达的变化。结果与假手术组及模型组相比,PA组,BK组,PA+BK组,IL-1β蛋白表达量明显增加(P<0.05);其中PA+BK组与其他各组相比,IL-1β蛋白表达量明显增高(P<0.01)。结论罂粟碱与缓激肽配伍应用对血肿瘤屏障开放具有协同效应。细胞因子IL-1β蛋白表达的变化趋势与血肿瘤屏障通透性的变化有关。Aim To investigate whether the annexation of bradykinin and papaverine had some synergetic effects on the opening of blood-tumor barrier, and find out the action of cytokine in this mechanism. Methods 160 female rats were divided into 8 groups：sham op erated group ; model group, PA group, BK group, PA ＋ BK group, 1/2PA ＋ BK group, I/2BK ＋ PA group and 1/2PA ＋ I/2BK group. 20 rats were needed in each group. The C6 brain tumor model was built. The drug was pumped into rat＇s brain via the carotid artery. The opening of the tight junction was detected by electron microscop. And the permeability of the blood-tumor barrier was tested by Evans blue. The expression of IL- 1β was tested by Western blot and the expression of IL-1β on/around the capillary in the brain of the cerebral glioma rats was tested by SABC immunochemistry. Results In contrast to sham operated group/model group,the expression of IL-1β in PA group, BK group and PA ＋ BK group increased obviously （ P 〈 0. 05 ）. The expression of IL-1β in PA ＋ BK group increased significantly compared to other groups （ P 〈 0. 01 ）. Conclusions The annexation of bradykinin and papaverine had synergetic effects on the opening of the blood-tumor barrier. And the variance of the expression of IL-1β was consistent with the variance of the permeability of the blood-tumor barrier.

关 键 词：罂粟碱 缓激肽 白细胞介素-1Β 血肿瘤屏障 脑胶质瘤 

分 类 号：R-332[医药卫生] R322.12