广东药科大学学报2019，Vol.35Issue(1)：69-75,7.DOI:10.16809/j.cnki.2096-3653.2018121002
白果内酯通过Nrf2/HO-1信号通路改善氧化应激所致体外血脑屏障损伤的研究
Bilobalide attenuates in vitro blood-brain barrier damage caused by oxidative stress via Nrf2/HO-1 signaling pathway
摘要
Abstract
Objective To investigate the protective effect and mechanism of bilobalide on blood-brain barrier (BBB) injury induced by hydrogen peroxide (H2O2) in vitro. Methods The hCMEC/d3 cells and HEB cells were co-cultured to establish an in vitro BBB model. The model was divided into 6 groups, including the control group, H2O2 model group (500 μmol/L), three different doses of bilobalide groups (0.2, 1 and 5 μmol/L), and Edaravone (10 μmol/L) positive control group. Different concentrations of bilobalide and edaravone were used to pretreat the BBB model for 24 h, and H2O2 (500 μmol/L) was induced for 2 h to form an oxidative stress injury model. Cell viability assay was measured by cell counting Kit-8 (CCK-8). The levels of nitric oxide (NO), glutathione (GSH), lactate dehydrogenase (LDH) and total antioxidant capacity were detected in the BBB model. Transendothelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability were used to investigate BBB permeability. Western blotting was used to detect the expression of tight junction-associated proteins (claudin-5, occludin and VE-Cadherin) and antioxidant proteins (Nrf2 and HO-1). Results Oxidative stress increased the permeability of the in vitro BBB and down-regulated the expression of tight junction proteins. Pretreatment with bilobalide increased the total antioxidant capacity of endothelial cells, and NO and GSH levels, reduced LDH levels, maintained the normal BBB resistance and the lower sodium fluorescein permeation, relieved the down-regulation of the tight junction proteins, and up-regulated Nrf2/HO-1 pathway protein expression. Conclusion Bilobalide can protect the BBB permeability from oxidative stress damage through the antioxidant action mediated by Nrf2/HO-1 pathway.关键词
白果内酯/血脑屏障/氧化应激损伤/抗氧化能力Key words
bilobalide/blood-brain barrier/oxidative stress damage/antioxidant capacity分类
医药卫生引用本文复制引用
徐玮,梁文意,郭彩娟,黄亿健,李育平,贝伟剑,郭姣..白果内酯通过Nrf2/HO-1信号通路改善氧化应激所致体外血脑屏障损伤的研究[J].广东药科大学学报,2019,35(1):69-75,7.基金项目
国家自然科学基金项目(81473588) （81473588）
广东省重大专项(2013A022100041) （2013A022100041）
