Effect of HMG CoA reductase inhibitor on kidney allograft function

HMG CoA还原酶抑制剂对同种异体移植肾功能的影响

• 批准号: 12671565
• 负责人: CHIKARAISHI Tatsuya
• 金额: $ 2.11万
• 依托单位: St. Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671565/
• 关键词: Fluvastatin; Immunosupression; Mixed lymphocyte culture reaction; フルバスタチン; リンパ球混合培養; 免疫抑制; 高脂血症; HMGCoARI

We investigated the potential role of fluvastatin(FV) in mitogen induced or allogeneic lymphocyte proliferative reactions in vitro.<Materials and methods> Human peripheral blood lymphocytes were co-cultured with I12, PHA, or allogeneic lymphocytes in microcultureplate. FV was administered to each well at a final concentration of 2, 10, 50, 100 and 150ng/ml. The uptake of 3H-labeled thymidine was counted to estimate lymphocyte proliferation.<Results> FV did not suppress the IL2 induced lymphocyte proliferation with the CPM value of 6942.7 ± 912.2(FV=2ng/ml), 8493.7 ± 1967.3(FV=10ng/ml), 6482 ± 3126.7(FV=50ng/ml), 7976.3 ± 2063.9(FV=100ng/ml), 3903 ± 2591.4(FV=150ng/ml). FV did not suppress the PHA induced lymphocyte proliferation with the CPM value of 26930 ± 11448.6(FV=0), 31048.33 ± 7619.4(FV=2), 25309.7 ± 9573.4(FV=10), 31613 ± 8745.9(FV=50), 23643.3 ± 4605.2(FV=100), 14290.3 ± 8405.4(FV=150). FV did not suppress alogeneic stimulation test (responder A against inactivated stimulator B) with the CPM value of 9848.3 ± 4580.3(FV=0), 107640 ± 3659.3(FV=2), 10898.7 ± 888.3(FV=10), 7599.3 ± 1084.7(FV=50), 5140.3 ± 501.4(FV=100), 7257.7 ± 3945.9(FV=150), however, FV more than 50 ng/ml significantly suppressed the allogeneic stimulation test in a different combination of responder B against inactivated stimulator A with CPM value of 16202.2 ± 2733.8(FV=0), 17952.3 ± 5363.5(FV=2), 13898.3 ± 3033.6(FV=10), 9169 ± 3902.9(FV=50), 8170.3 ± 2598.9(FV=100), 7981.3 ± 2481.7(FV=150). <Conclusion> FV did not suppress the mitogen induced lymphocyte proliferation, however, may have suppressive effect on allogeneic lymphocyte stimulation.

本研究探讨了氟伐他汀（FV）在体外有丝分裂原诱导或同种异体淋巴细胞增殖反应中的潜在作用。<Materials and methods>将人外周血淋巴细胞与I12、PHA或同种异体淋巴细胞在微量培养板上共培养。将FV以2、10、50、100和150 ng/ml的终浓度施用至每个孔。计数3 H标记的胸苷的摄取以估计淋巴细胞增殖。<Results>FV对IL 2诱导的淋巴细胞增殖无抑制作用，CPM值分别为6942.7 ± 912.2（FV=2ng/ml）、8493.7 ± 1967.3（FV= 10 ng/ml）、6482 ± 3126.7（FV= 50 ng/ml）、7976.3 ± 2063.9（FV= 100 ng/ml）、3903 ± 2591.4（FV= 150 ng/ml）。FV对PHA诱导的淋巴细胞增殖无抑制作用，CPM值分别为26930 ± 11448.6（FV=0），31048.33 ± 7619.4（FV=2），25309.7 ± 9573.4（FV=10），31613 ± 8745.9（FV=50），23643.3 ± 4605.2（FV=100），14290.3 ± 8405.4（FV=150）。FV对同种异体刺激试验无抑制作用（应答者A对失活刺激物B），CPM值为9848.3 ± 4580.3（FV=0）、107640 ± 3659.3（FV=2）、10898.7 ± 888.3（FV=10）、7599.3 ± 1084.7（FV=50）、5140.3 ± 501.4（FV=100），7257.7 ± 3945.9（FV=150），然而，大于50 ng/ml的FV显著抑制了应答者B与失活刺激物A的不同组合中的同种刺激测试，CPM值为16202.2 ± 2733.8（FV=0）、17952.3 ± 5363.5（FV=2）、13898.3 ± 3033.6（FV=10）、9169 ± 3902.9（FV=50）、8170.3 ± 2598.9（FV=100）、7981.3 ± 2481.7（FV=150）。<Conclusion>FV对丝裂原诱导的淋巴细胞增殖无抑制作用，但对同种异体淋巴细胞刺激有抑制作用。

项目成果

Chikaraishi T, Satoh Y, Tsutumi T, Miyano S, Matsushita T, Nozawa S, Iwamoto T and Takahashi G: "Effect of Fluvastatin, an HMG CoA reductase inhibitor, on lymphocyte proliferative reaction in vivo"Jpn. J. Transplantation. 37. 193-197 (2002)

Chikaraishi T、Satoh Y、Tsutumi T、Miyano S、Matsushita T、Nozawa S、Iwamoto T 和 Takahashi G：“HMG CoA 还原酶抑制剂氟伐他汀对体内淋巴细胞增殖反应的影响”Jpn。

Chikaraishi T, Iwamoto T, Hoshino T, Makizumi K, Yanagisawa N, Furuhata S, Sasaki H, Kato K and Inoue M: "Aulologous blood transfusion for kidney transplant recipients"Transplantation proceedings. 32. 1853-1854 (2000)

Chikaraishi T、Iwamoto T、Hoshino T、Makizumi K、Yanagisawa N、Furuhata S、Sasaki H、Kato K 和 Inoue M：“肾移植受者的同体输血”移植程序。

Chikaraishi T.,Iwamoto T.,Hoshino T.,Makizumi K.,Yanagisawa N.,Furuhata S.,Sasaki H.,Kato K.,and Inoue M.: "Autologous blood transfusion for kidney transplant recipients"Transplantation Proceedings. 32. 1853-1854 (2000)

Chikaraishi T.、Iwamoto T.、Hoshino T.、Makizumi K.、Yanagisawa N.、Furuhata S.、Sasaki H.、Kato K.和 Inoue M.：“肾移植受者的自体输血”移植论文集。

力石辰也, 佐藤裕子, 堤 久, 宮野佐哲, 松下知彦, 野澤資亜利, 岩太昇明, 高橋剛: "高脂血症治療薬フルバスタチンの免疫抑制効果の検討-第1報-"移植. 37. 193-197 (2002)

Tatsuya Chikaraishi、Yuko Sato、Hisashi Tsutsumi、Satetsu Miyano、Tomohiko Matsushita、Shiari Nozawa、Noboaki Iwata、Tsuyoshi Takahashi：“治疗高脂血症的药物氟伐他汀的免疫抑制作用研究 - 第 1 次报告 -” 37. 193 -197 (2002)

Chikaraishi T., Iwamoto T., Hoshino T., Makizumi K., Yanagisawa N., Furuhata S., Sasaki H., Kato K., Inoue M.: "Autologous blood transfusion for kidney transplant recipients"Transplantation Proceedings. 32. 1853-1854 (2000)

Chikaraishi T.、Iwamoto T.、Hoshino T.、Makizumi K.、Yanagisawa N.、Furuhata S.、Sasaki H.、Kato K.、Inoue M.：“肾移植受者的自体输血”移植论文集。