目的：观察银杏内酯和银杏黄酮干预β－淀粉样蛋白（Aβ）跨血脑屏障（BBB）低氧模型的转运情况及与晚期糖基化终产物受体（RAGE）、低密度脂蛋白受体相关蛋白1（LRP1）表达的相关性。方法利用 Tran－swell 装置共培养大鼠脑微血管内皮细胞与星形胶质细胞建立 BBB 模型，并分为对照组、低氧模型组、银杏内酯组、银杏黄酮组及联合用药组。观察 Aβ由脑侧向血管侧的转运情况，并检测 TEER 值及 FD4通透率以评价 BBB完整性，采用 RT －qPCR 及 Western blot 法检测转运体 RAGE、LRP1的表达。结果在低氧条件下，受试药物单独或联合干预后，Aβ的外向转运率明显上升，差异有统计学意义，且联合用药效果更优。各组处理均未破坏 BBB 的完整性；低氧上调 RAGE 的表达，下调 LRP1的表达，药物单独干预均能改善低氧对 LRP1的抑制作用，但不影响RAGE 的表达；而联合用药下调 RAGE 表达，同时上调 LRP1表达。结论银杏叶活性成分银杏内酯和银杏黄酮通过干预 BBB 低氧模型 RAGE 及 LRP1的表达，促进 Aβ的外向转运，从而降低脑 Aβ水平，延缓了阿尔茨海默病的进展。%Objective To observe the effects of glingolide and ginkgo flavone on β-amlyoid (Aβ) transcytosis across the blood -brain barrier (BBB) in hypoxic condition and its correlation with BBB transporter RAGE and LRP1. Methods The BBB models were established by co -culturing rat brain microvascular endothelial cells and astrocytes in vitro in the Transwell device, and divided into control group, hypoxic group, Glingolide or Ginkgo Flavone alone and com-bined treatment groups.The basolateral -to -apical permeability of Aβwas detected by using enzyme -linked immu-nosorbent assay (ELISA).The BBB integrity was evaluated by measuring transepithelial -astocyte electrical resistance (TEER) and FD4 permeability rate.The expression of RAGE and LRP1 was assessed by RT -qPCR and Western blot. Results The efflux rate of Aβacross the BBB under hypoxic condition was lower compared with that in the control group. The efflux rate of Aβwas significantly increased after application of glingolide and/or ginkgo flavone.The BBB integrity was not damaged with any treatments.RAGE expression was up -regulated while LRP1 expression was down -regulated under hypoxic condition.Administration of any single compound enhanced the inhibitory effect of low oxygen on LRP1 without affecting RAGE.The RAGE was down -regulated but LRP1 was up -regulated in combined treatment.Conclu-sion Glingolide and ginkgo flavone can promote Aβefflux through intervening RAGE and LRP1 expression to delay the development of Alzheimer′s disease.
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