An Ping, Xue Yi-Xue
Department of Neurobiology, College of Basic Medicine, China Medical University, No. 92 Second Road Heping District, Shenyang 110001, PR China.
Brain Res. 2009 May 26;1272:81-8. doi: 10.1016/j.brainres.2009.03.031. Epub 2009 Mar 28.
Brain ischemia can usually disrupt the blood-brain barrier (BBB), increasing the permeability of BBB. Ischemic preconditioning could not only reduce neurons damage, but also protect the functions of BBB during brain ischemia. In this study, we used BBB model in vitro to examine the effects of preconditioning on cell viability, BBB permeability, tight junction and cell adhesion of rat brain microvascular endothelial cells (BMECs). The rat BMECs were exposed to 2.5 h of oxygen glucose deprivation (OGD) following 3 h of reoxygenation to simulate ischemia/reperfusion in vivo, using 0.5 h OGD as preconditioning. Results showed that OGD/reoxygenation induced cell death, increased BBB permeability, changed the distribution of endothelial cells tight junction protein ZO-1 and cellular framework protein F-actin, and increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). OGD preconditioning could partially protect cell viability and BBB permeability, maintain the membrane location of ZO-1 and F-actin, and decrease the expression of ICAM-1 and VCAM-1. Our study suggests that OGD preconditioning could stabilize the tight junction protein and alleviate cell adhesion to protect BBB function during ischemic stress.
脑缺血通常会破坏血脑屏障(BBB),增加血脑屏障的通透性。缺血预处理不仅可以减少神经元损伤,还能在脑缺血期间保护血脑屏障的功能。在本研究中,我们使用体外血脑屏障模型来检测预处理对大鼠脑微血管内皮细胞(BMECs)的细胞活力、血脑屏障通透性、紧密连接和细胞黏附的影响。将大鼠BMECs先进行3小时复氧,然后暴露于2.5小时氧糖剥夺(OGD)以模拟体内缺血/再灌注,以0.5小时OGD作为预处理。结果显示,OGD/复氧诱导细胞死亡,增加血脑屏障通透性,改变内皮细胞紧密连接蛋白ZO-1和细胞骨架蛋白F-肌动蛋白的分布,并增加细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的表达。OGD预处理可部分保护细胞活力和血脑屏障通透性,维持ZO-1和F-肌动蛋白的膜定位,并降低ICAM-1和VCAM-1的表达。我们的研究表明,OGD预处理可稳定紧密连接蛋白并减轻细胞黏附,以在缺血应激期间保护血脑屏障功能。