Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance

炎症细胞因子对肾小管药物转运蛋白功能的调节及其意义

• 批准号: 23590180
• 负责人: OKUDA Masahiro
• 金额: $ 3.33万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590180/
• 关键词: メトトレキサート; リポ多糖; ラット; 有機アニオントランスポータ; 腎クリアランス; サイトカイン; リポポリサッカライド; 腎尿細管; 尿細管分泌; 炎症; 尿細管分泌クリアランス

Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.

在通过给予脂多糖(LPS)制备的炎症大鼠模型中，甲氨蝶呤(MTX)的血浆清除率降低了约50%。 LPS 降低 MTX 的肾脏清除率表明肾小球滤过和肾小管分泌参与其中。 LPS 大鼠的肾组织/血浆浓度比和从肾组织到肾小管腔的流出清除率也降低，与肾脏中有机阴离子转运蛋白（rOAT1、rOAT3、rMRP2、rMRP4）表达水平的降低相当。 总之，LPS 处理的大鼠中 MTX 的肾脏清除率显着降低，这表明肾小球滤过率降低以及肾小管中有机阴离子转运蛋白表达水平降低。

项目成果

miR-145による小腸上皮細胞P-糖蛋白質の転写後発現調節機構

miR-145对小肠上皮细胞P-糖蛋白转录后表达调控机制

• 发表时间: 2013
• 作者: 池村健治;山本弥里;宮崎さおり;水谷秀樹;岩本卓也;奥田真弘
• 通讯作者: 奥田真弘

Altered Pharmacokinetics of Cimetidine Caused by Down-regulation of Renal Rat Organic Cation Transporter 2 (rOCT2) after Liver Ischemia-Reperfusion Injury

• DOI: 10.2133/dmpk.dmpk-13-rg-021
• 发表时间: 2013-12-25
• 期刊: DRUG METABOLISM AND PHARMACOKINETICS
• 影响因子: 2.1
• 作者: Ikemura, Kenji;Nakagawa, Erika;Okuda, Masahiro
• 通讯作者: Okuda, Masahiro

Evaluation of Basophil CD203c as a Predictor of Carboplatin-Related Hypersensitivity Reaction in Patients with Gynecologic Cancer

• DOI: 10.1248/bpb.b12-00150
• 发表时间: 2012-09-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Iwamoto, Takuya;Yuta, Atsushi;Okuda, Masahiro
• 通讯作者: Okuda, Masahiro

虚血再灌流障害時における酸化ストレスを介した小腸CYP3A及びP-糖蛋白質の発現上昇によるcyclosporine Aの経口吸収低下

缺血再灌注损伤期间氧化应激导致小肠 CYP3A 和 P-糖蛋白表达增加，导致环孢素 A 口服吸收减少

• 发表时间: 2011
• 作者: 池村健治;水谷秀樹;岩本卓也;奥田真弘
• 通讯作者: 奥田真弘

マイクロRNA145(miR-145)によるMDR1/P-糖タンパク質(P-gp)の転写後発現調節

microRNA145 (miR-145) 对 MDR1/P-糖蛋白 (P-gp) 的转录后表达调控

• 发表时间: 2012