Department of Neurobiology, College of Basic Medicine, China Medical University, 110001 Shenyang, Liaoning Province, People's Republic of China.
J Neurooncol. 2010 Sep;99(2):187-94. doi: 10.1007/s11060-010-0124-x. Epub 2010 Feb 10.
Bradykinin (BK) increases the permeability of the blood-tumor barrier (BTB) selectively through the transcellular pathway; however, the role of the caveolae structural proteins caveolin-1 and caveolin-2 in this process has not been precisely elucidated. Thus, this study was performed to examine whether caveolin-1 and caveolin-2 are involved in the regulation of this biological process. In the rat brain glioma (C6) model, western blot, immunohistochemistry, and immunofluorescence assays were used to detect the expression levels and locations of caveolin-1 and caveolin-2. The results showed that caveolin-1 and caveolin-2 levels increased 5 min after BK infusion, peaked at 15 min, and then decreased. Meanwhile, Evans blue (EB) assay showed that the permeability of the BTB increased significantly after BK infusion. In our previous study we demonstrated that the quantity of pinocytotic vesicles in the endothelial cells was dramatically augmented 15 min after BK infusion. The time point at which changes of caveolin-1 and caveolin-2 reached their peak was the same as that at which EB and the quantity of pinocytotic vesicles reached their peaks. This led to the conclusion that the BK-mediated BTB permeability increase resulting from augmentation of the quantity of pinocytotic vesicles (transcellular pathway) is associated with the significantly up-regulated expression of caveolin-1 and caveolin-2. This study thus contributes further to elucidating the molecular mechanism of opening of the BTB by BK and provides a theoretical basis for clinical application of BK.
缓激肽（BK）通过细胞旁途径选择性增加血脑肿瘤屏障（BTB）的通透性；然而，网格蛋白-1 和网格蛋白-2 等 caveolae 结构蛋白在该过程中的作用尚未得到精确阐明。因此，本研究旨在探讨 caveolin-1 和 caveolin-2 是否参与调节这一生物学过程。在大鼠脑胶质瘤（C6）模型中，采用 Western blot、免疫组织化学和免疫荧光检测 caveolin-1 和 caveolin-2 的表达水平和定位。结果显示，BK 输注后 5 min 时 caveolin-1 和 caveolin-2 水平升高，15 min 时达到峰值，随后下降。同时，Evans 蓝（EB）测定显示，BK 输注后 BTB 的通透性显著增加。在我们之前的研究中，我们证明了 BK 输注 15 min 后内皮细胞中胞饮小泡的数量显著增加。caveolin-1 和 caveolin-2 变化达到峰值的时间与 EB 和胞饮小泡数量达到峰值的时间相同。这表明，BK 介导的 BTB 通透性增加，导致胞饮小泡数量增加（细胞旁途径），与 caveolin-1 和 caveolin-2 的表达显著上调有关。因此，本研究进一步阐明了 BK 开放 BTB 的分子机制，为 BK 的临床应用提供了理论基础。
