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迷迭香酸干预PI3K/Akt信号通路保护缺氧/复氧损伤血脑屏障功能的影响
陈鹏1, 瞿晶田1, 王婧斯2
1.天津中医药大学第一附属医院, 天津 300193;2.盈科瑞(天津)创新医药研究有限公司, 天津 300385
摘要:
[目的] 考察迷迭香酸对缺氧/复氧损伤血脑屏障功能的影响并探讨作用机制。[方法] 通过单层血脑屏障体外模型,考察药物对细胞活力、乳酸脱氢酶漏出率、跨细胞间电阻值、异硫氰酸荧光素-葡聚糖透过率的变化,同时分析相应关键信号分子的变化。[结果] 与正常对照组比较,缺氧/复氧损伤可导致细胞活力降低,乳酸脱氢酶漏出增加,跨细胞间电阻值降低,异硫氰酸荧光素-葡聚糖透过率增加,罗丹明123(Rh123)蓄积增多,提示缺氧/复氧损伤条件下内皮屏障功能受损。给予迷迭香酸后血脑屏障功能明显改善,分子信号显著上调。[结论] 迷迭香酸可通过激活PI3K/Akt信号通路发挥保护缺氧/复氧损伤的血脑屏障功能的作用。
关键词:  迷迭香酸  血脑屏障功能  缺氧/复氧  PI3K/Akt信号通路
DOI:10.11656/j.issn.1672-1519.2021.03.23
分类号:R285.5
基金项目:国家自然科学基金青年项目(81603648)。
Effect of rosmarinic acid on PI3K/Akt signal pathway in protecting blood-brain barrier function by hypoxia/reoxygenation injury
CHEN Peng1, QU Jingtian1, WANG Jingsi2
1.First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;2.Increasepharm(Tianjin) Institnte Co. Ltd, Tianjin 300385, China
Abstract:
[Objective] To investigate the effect of rosmarinic acid (RA) on blood-brain barrier (BBB) function induced by hypoxia/reoxygenation and its mechanism.[Methods] The changes of cell viability, lactate dehydrogenase leakage rate, transcellular electrical resistance, and fluorescein isothiocyanate glucan permeability were investigated by the monolayer blood-brain barrier model in vitro, and the changes of key signal molecules were analyzed.[Results] Hypoxia/reoxygenation injury can result in decreased cell viability, increased LDH leakage, decreased TEER value, increased FITC-glucan permeability, increased Rh123 accumulation. RA can significantly improve the above injury and maintain BBB function. After administration of RA, the BBB function was significantly improved, and the molecular signal was significantly up-regulated.[Conclusion] RA has protective effect on BBB function in hypoxia/reoxygenation injury, and may be related to its intervention on PI3K/Akt signaling pathway.
Key words:  rosmarinic acid  blood-brain barrier function  hypoxia/reoxygenation  PI3K/Akt signaling pathway
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