Involvement of prostaglandin transport system at the blood-brainbarrier in the drug-induced vascular disorder in the brain.

血脑屏障处的前列腺素转运系统参与药物引起的大脑血管疾病。

• 批准号: 20790127
• 负责人: ITO Shingo
• 金额: $ 2.75万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790127/
• 关键词: 薬物動態学; 血液脳関門; プロスタグランディンE2; 薬物相互作用; プロスタグランディン; NSAIDs

Using Brain Efflux Index method, prostaglandin E2 (PGE2) was eliminated from mouse brain with a half-life of 12 minutes. By contrast, PGE2 increased brain capillary endothelial cell proliferation and slightly recovered from NASIDs mediated cytotoxicity. These results demonstrate that BBB efflux transport system is involved in the PGE2 clearance in mouse brain and suggest that PGE2 stimulate vascularization and remodeling of brain capillary endothelial cells and NSAIDs itself exert significantly cytotoxicity against brain capillary endothelial cells. Therefore, NSAIDs mediated reduction of PGE2 clearance and cytotoxicity against brain capillary endothelial cells may cause severe angiopacy in brain inflammation.

使用脑外排指数法，前列腺素E2（PGE2）从小鼠大脑中以半衰期为12分钟消除。相比之下，PGE2增加了脑毛细血管内皮细胞增殖，并从鼻动物介导的细胞毒性中稍微回收。这些结果表明，BBB外排运输系统参与了小鼠大脑中的PGE2清除率，并表明PGE2刺激脑毛细管内皮细胞的血管形成和重塑，NSAID本身对脑毛细管内皮细胞的细胞毒性显着施加。因此，NSAIDS介导了针对脑毛细管内皮细胞的PGE2清除率和细胞毒性的降低，可能会导致脑部炎症中严重的血管疾病。

项目成果

Involvement of Multidrug Resistance-Associated Protein 4 in Efflux Transport of Prostaglandin E2 across Mouse Blood-Brain Barrier and Its Inhibition by Intravenous Administration of Cephalosporins

• DOI: 10.1124/jpet.109.165332
• 发表时间: 2010-06-01
• 期刊: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
• 影响因子: 3.5
• 作者: Akanuma, Shin-ichi;Hosoya, Ken-ichi;Ohtsuki, Sumio
• 通讯作者: Ohtsuki, Sumio