免疫抑制剤治療における白血球P-糖蛋白質の役割解明と臨床応用

阐明白细胞P-糖蛋白在免疫抑制剂治疗中的作用及临床应用

• 批准号: 12877383
• 负责人: 乾 賢一
• 金额: $ 1.54万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Exploratory Research
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12877383/
• 关键词: P-糖蛋白質; 免疫抑制剤; タクロリムス; 白血球; 薬効発現; 臓器移植; 薬物輸送

シクロスポリンやタクロリムス(FK506)は、臓器移植手術後の拒絶反応抑制薬として繁用されているが、これら免疫抑制剤の薬効発現に着目した薬物使用指針に関する情報はほとんどない。本研究では、これら免疫抑制剤の標的臓器への分布、すなわち末梢白血球への移行性を定量的に予測し、臓器移植患者個々に至適な投与設計を提供しうる新規薬物治療支援システムの開発を目指した。先ず、末梢白血球に発現するP-糖蛋白質発現量の数値定量化を試みた。無作為に抽出した19例の生体肝移植レシピエント患者について、術後のタクロリムス血中濃度測定用に採取された血液検体の余剰分を用いて末梢白血球由来のtotal RNAの抽出とP-糖蛋白質をコードするMDR1 mRNA発現量の定量を行った。その結果、白血球のP-糖蛋白質の発現量は個体間で大きく異なること、個体内でも大きく変動しうることが明らかとなった。次に、それぞれの患者におけるタクロリムスの維持血中濃度と白血球P-糖蛋白質の発現量との比較解析を行ったところ、白血球P-糖蛋白質の発現量が高い患者ではタクロリムスの維持血中濃度が高い傾向が認められた。現在、症例数を増やして白血球に発現するP-糖蛋白質の発現量と免疫抑制剤の薬効発現との関係について解析を継続している。

After the transplant of the hand, the device was used to suppress the frequent use of FK506, immunosuppression, immunosuppression, and the use of fingertips. In this study, the device distribution of immunosuppressive mice, the quantitative administration of peripheral white blood cells (WBC) in immunosuppressive mice, and the treatment and design of transplant patients were provided to support the treatment of immunosuppressive drugs. First, the peripheral white blood cell assay showed that the amount of P-glycoprotein was measured by quantitative assay. In order to extract the blood samples of 19 patients with severe liver transplantation, the blood samples were collected, the rest of the samples were collected, and the peripheral white blood cells were extracted by total RNA. The amount of MDR1 mRNA was measured by quantitative assay. The results showed that the amount of white blood cell P-glycoprotein was measured in two groups, one in vivo, one in vivo, one in vivo and one in vivo. In the second and third trimester, the patients were divided into two groups: the level of white blood cell P-glycoprotein, the level of white blood cell P At present, the number of cases, white blood cell count, P-glycoprotein concentration, immunosuppression, immunosuppression, immune suppression, leukocyte count, immune suppression, leukocyte count, leukocyte count, P-glycoprotein antibody, immune suppression, leukocyte count, leukocyte count, immune suppression, immune suppression, leukocyte count, leukocyte count, immune suppression, leukocyte count, leukocyte count, immune suppression, leukocyte count, leukocyte count, immune suppression, immunosuppression, immune suppression, leukocyte count, immune suppression, leukocyte count, leukocyte count, immune suppression, immune suppression, leukocyte count, leukocyte count, immune suppression, immune suppression, leukocyte count, leukocyte count, immune suppression, immune suppression, leukocyte count, leukocyte count

项目成果

H.Motohashi et al.: "Expression of peptide transporter following intestinal transplantation in the rat"J Surg Res. (In press). (2001)

H.Motohashi 等：“大鼠肠移植后肽转运蛋白的表达”J Surg Res。

S.Masuda et al.: "Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient"Clin Pharmacol Ther. 68・1. 98-103 (2000)

S. Masuda 等：“肠道 P 糖蛋白对活体小肠受者每日他克莫司谷值的影响”Clin Pharmacol Ther 68・1 (2000)。

T.Hashida et al.: "Pharmacokinetic and Prognostic Significance of Intestinal MDR1 Expression in Recipients of Living-donor Liver Transplantation"Clin Pharmacol Ther. (In press). (2001)

T.Hashida 等：“活体肝移植受者肠道 MDR1 表达的药代动力学和预后意义”Clin Pharmacol Ther。