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三磷酸腺苷敏感性钾通道激活剂诱导大鼠脑肿瘤模型中窖蛋白-1的表达上调。

Adenosine 5'-triphosphate-sensitive potassium channel activator induces the up-regulation of caveolin-1 expression in a rat brain tumor model.

机构信息

Department of Physiology, Life Science and Biology Pharmacopedia Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, People's Republic of China.

出版信息

Cell Mol Neurobiol. 2011 May;31(4):629-34. doi: 10.1007/s10571-011-9658-5. Epub 2011 Feb 18.

Abstract

This study was performed to determine whether minoxidil sulfate (MS), a selective Adenosine 5'-triphosphate-sensitive potassium channel (K (ATP) channel) activator, has an effect on the expression of caveolin-1 in the rat's brain tumor tissue. Using a rat brain glioma (C6) model, we found that the expression of caveolin-1 protein at tumor sites was greatly increased after intracarotid infusion of MS at a dose of 30 μg/kg/min for 15, 30, and 60 min via Western blot analysis. And the peak value of the caveolin-1 expression was observed in rats with glioma after 15 min of MS perfusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of blood-brain tumor barrier (BTB) permeability which was induced by MS. This led to the conclusion that the MS-induced BTB permeability increase may be related to the accelerated formation of caveolin-1 protein, and could be mediated by ROS.

摘要

本研究旨在确定硫酸米诺地尔(MS),一种选择性的三磷酸腺苷敏感钾通道(KATP 通道)激活剂,是否对大鼠脑肿瘤组织中窖蛋白-1的表达有影响。通过大鼠脑胶质瘤(C6)模型,我们发现经颈内动脉内输注 MS(剂量为 30μg/kg/min)15、30 和 60min 后,Western blot 分析显示肿瘤部位的窖蛋白-1 蛋白表达显著增加。并且在 MS 灌注 15min 后,荷瘤大鼠的窖蛋白-1 表达达到峰值,而过氧化氢(ROS)清除剂(N-2-巯基丙酰甘氨酸,MPG)显著减弱了这种增加。此外,MPG 还显著抑制了 MS 诱导的血脑肿瘤屏障(BBTB)通透性增加。这表明 MS 诱导的 BTB 通透性增加可能与窖蛋白-1 蛋白的加速形成有关,并且可能由 ROS 介导。

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