Zhang Sai, Liu Yunhui, Zhao Zhen, Xue Yixue
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang China.
Neurol Res. 2010 Nov;32(9):963-70. doi: 10.1179/016164110X12700393823570. Epub 2010 May 4.
This study was designed to investigate the effects of green tea polyphenols (GTPs) on the permeability of blood-brain barrier (BBB), and the expression of caveolin-1 and extracellular signal-regulated kinase ½ (ERK1/2) after cerebral ischemia.
Cerebral ischemia was established by middle cerebral artery occlusion (MCAO). Rats were randomly divided into control and GTP groups, and both included four time points of interest: MCA occluded for 0 hour, 1 hour, 2 hours, and 4 hours groups. After ischemia, triphenyltetrazolium chloride staining and Longa's score were used to determine the infarct volume and neurological deficit. Evans blue (EB) content in the brain tissue was measured to observe the BBB permeability. RT-PCR, immunohistochemistry, and western blot assessment were used to detect expression of caveolin-1 in microvessel fragments of cerebral ischemic tissue. Western blot was also used to examine ERK1/2.
GTPs significantly reduced infarct volume, ameliorated the neurological deficit, and reduced the permeability of BBB. GTPs also obviously reduced the levels of caveolin-1 mRNA and protein expression as well as the expression of phosphorylated ERK1/2 in microvessel fragments of cerebral ischemic tissue, which were enhanced by cerebral ischemia.
These data were the first to show that GTPs can decrease the elevated BBB permeability in the ischemic region, and the protective effects for cerebral injury may be related to the reduced expression of caveolin-1 and phosphorylated ERK1/2.
本研究旨在探讨绿茶多酚(GTPs)对脑缺血后血脑屏障(BBB)通透性以及小窝蛋白-1和细胞外信号调节激酶1/2(ERK1/2)表达的影响。
通过大脑中动脉闭塞(MCAO)建立脑缺血模型。将大鼠随机分为对照组和GTP组,每组均包含4个感兴趣的时间点:大脑中动脉闭塞0小时、1小时、2小时和4小时组。缺血后,采用氯化三苯基四氮唑染色和Longa评分来确定梗死体积和神经功能缺损。测量脑组织中伊文思蓝(EB)含量以观察血脑屏障通透性。采用逆转录-聚合酶链反应(RT-PCR)、免疫组织化学和蛋白质印迹法评估检测脑缺血组织微血管片段中小窝蛋白-1的表达。蛋白质印迹法还用于检测ERK1/2。
GTPs显著减小梗死体积,改善神经功能缺损,并降低血脑屏障通透性。GTPs还明显降低脑缺血组织微血管片段中小窝蛋白-1 mRNA和蛋白表达水平以及磷酸化ERK1/2的表达,而脑缺血会使其表达增强。
这些数据首次表明,GTPs可降低缺血区域升高的血脑屏障通透性,其对脑损伤的保护作用可能与小窝蛋白-1和磷酸化ERK1/2表达降低有关。