Blood-brain barrier breakdown by PAF and protection by XQ-1H due to antagonism of PAF effects.
European Journal of Pharmacology(2009)
摘要
Hypoxia and reoxygenation set in motion a series of events, including blood-brain barrier breakdown. We examined the content and effect of platelet-activating factor (PAF), which was increased in the rat brain microvessel endothelial cells (RBMECs) during hypoxia and reoxygenation. MTT method was used to assay cell damage; ELISA analysis was used to estimate PAF release after hypoxia and reoxygenation injury; and RT-PCR and Western blotting method were used to assess gene and protein expressions of inducible nitric-oxide synthase (iNOS) in RBMECs under PAF damage. PAF affected intracellular free Ca2+ levels, increasing [Ca2+]i, which caused up-regulation of iNOS. We also examined the blood-brain barrier protective effect of XQ-1H, a novel ginkgolide B derivative. Pretreatment with XQ-1H (10 µM and 3 µM) for 24 h significantly antagonized PAF receptor and inhibited the increase in intracellular calcium concentration and the up-regulation of iNOS in response to PAF under hypoxia and reoxygenation in vitro.
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关键词
Hypoxia,Reoxygenation,RBMEC (rat brain microvessel endothelial cell),PAF (platelet-activating factor),XQ-1H
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