期刊
ACTA NEUROPATHOLOGICA
卷 116, 期 5, 页码 529-535出版社
SPRINGER
DOI: 10.1007/s00401-008-0435-6
关键词
Hypoxia hypoglycemia; Cerebral microvascular endothelial cells; LRP-1; RAGE; EGb 761
资金
- Natural Science Foundation of Southeast University [XJ0590215]
Alzheimer's disease (AD), characterized by accumulation of amyloid-beta protein (A beta) in brain parenchyma, is closely associated with brain ischemia. Decreased clearance of A beta from brain is the main cause of A beta accumulation in sporadic AD. However, the mechanisms underlying ischemia-mediated AD pathogenesis remain unclear. The receptor for advanced end glycation products (RAGE) and low-density lipoprotein receptor-related protein-1 (LRP-1) expressed at blood brain barrier (BBB) are actively involved in A beta clearance. RAGE is thought to be a primary transporter of A beta across BBB into the brain from the systemic circulation, while LRP-1 mediates the transport of A beta out of the brain. Ginkgo biloba extract EGb761, a traditional Chinese medicine, has been widely used in the treatment of AD. To investigate the effects of EGb761 on the expression of RAGE and LRP-1 in endothelial cells in response to ischemic injury, we cultured bEnd.3 cells, an immortalized mouse cerebral microvessel endothelial cell line, under a chronic hypoxic and hypoglycemic condition (CHH) to mimic ischemic injury of BBB, and then treated with EGb 761. We found that EGb 761 markedly ameliorated the damage (evaluated by MTT assay) from CHH. Moreover, we demonstrated that CHH led to a significant increase in the expression of RAGE both at the mRNA and protein levels at all times (24, 36, and 48 h), conversely; CHH induced a dramatic decrease in LRP-1 mRNA and protein expression at both 36 and 48 h. The results indicated that CHH has differential effects on the expression of RAGE and LRP-1. Furthermore, EGb761 significantly reversed CHH-induced upregulation of RAGE expression and downregulation of LRP-1 expression. Our findings suggest that EGb761 favor clearance of A beta via regulating the expression of RAGE and LRP-1 during brain ischemia. This may provide a new insight into a possible molecular mechanism underlying brain ischemia-mediated AD pathogenesis, and potential therapeutic application of EGb 761 in treatment of AD.
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