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Development of new preservation solution to maintain vascular endothelial Integlity.

Research Project

Project/Area Number 13557101
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Digestive surgery
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

JIN Maeng bong (2002-2003)  Hokkaido Univ., Grad. School of Med., Corporate Donated Chair Teacher, 大学院・医学研究科, 寄附講座教員 (40333603)

山本 浩史 (2001)  北海道大学, 大学院・医学研究科, 助手 (50312351)

Co-Investigator(Kenkyū-buntansha) SHIMAMURA Tsuyoshi  Hokkaido Univ., Hokkaido University hospital, Lec., 医学部・歯学部附属病院, 助手 (00333617)
FURUKAWA Hiroyuki  Hokkaido Univ., Grad. School of Med., Corporate Donated Chair Teacher, 大学院・医学研究科, 寄附講座教員 (70292026)
TODO Satoru  Hokkaido Univ., Grad. School of Med., Pro., 大学院・医学研究科, 教授 (60136463)
KURAUCHI Nobuaki  Hokkaido Univ., Hokkaido University hospital, Lec., 医学部・歯学部附属病院, 助手 (70322815)
松下 通明  北海道大学, 医療技術短期大学部, 教授 (20250425)
陳 孟鳳  北海道大学, 大学院・医学研究科, 寄付講座教員 (40333603)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
KeywordsRho / Y-27632 / edaravone / HTK / NAG / Cr / FENa / MDA / ET-1 / 尿中NAG / HTK液 / Rho-Kinase / 肝温阻血障害 / ICAM-1 / アデノシン / サイクリックAMP / アデニレートサイクラーゼ / ホスホジエステラーゼIII / アムリノン / ミルリノン / オロプリノン
Research Abstract

A. The effect of vaso-reactive substances on the organ preservation were investigated. Vaso-active substances could reduce neutrophil infiltration into reperfused liver tissue. They also promoted the maintenance of hepatic tissue blood flow even after 2hr complete hepatic warm ischemia using total hepatic vascular occlusion model. Moreover, they attempted remarkable recovery of hepatic energy metabolism.
B. For example, we tried a brand new Rho-associated protein kinase, Y 27632 to prove that Rho-kinase can play a key role even in the hepatic ischemia reperfusion injury. Male SD rats were engaged in a 70% partial hepatic ischemia model. Animals were divided into two groups, a no-treated group, a group treated with 10mg/kg Y-27632 p.o before 90 min warm ischemia, Survival, arterial pressure, hart rate, hepatic tissue blood flow, ALT, ET-1, Hyauronic acid, MPO activity, Mac-1 stain, and pathological history were investigated. The treatment ameliorated survival, hepatic tissue blood flow, ALT, ET-1, HA, and MPO, significantly, and also reduced the number of Mac-1 positive neutrophil infiltration into liver tissue.
C. A brand new substance, edaravone, was tested for its ability as a radical scavenger using canine kidney auto transplantation model after 72hr cold preservation in HTK solution. Animal were randomly divided into two groups, treated one and untreated control. Edaravone was infused systematically before graft procurment, given into preservation solution, and administered systematically after grafting. The treatment unproved urine volume, NAG/Cr, FENa, and lessened Cr level, acute tubular necrosis, and MDA level in kidney draft.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Masuko H: "Protective effect of angiotensin II type I receptor antagonist, CV-11974, on ischemia and reperfusion injury of the liver."Transplantation. 71(8). 1034-1039 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogata K: "Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type II phospholipase A_2 with LY329722."Transplantation. 71(8). 1040-1046 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishikawa H: "Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers"Transplantation. 73(7). 1041-1048 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda T: "A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats."Surgery. 133. 197-206 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 陳 孟鳳: "脳死肝移植における肝保存と阻血再灌流障害"臨床雑誌「外科」. 66. 148-154 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 陳 孟鳳: "肝移植のクリニカルパス"臨床外科. 58(11). 144-150 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 陳 孟鳳: "深尾 立編:大動物臓器移植実験マニュアル、多臓器移植イヌ"日本医学館、東京. 214 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masuko H, Jin MB, Horiuchi H, Suzuki T, Taniguchi M, Shimamura T, Fukai M, Magata S, Ogata K, Ishikawa H, Fujita M, Nagashima K, Furukawa H, Todo S: "Protective effect of angiotensin type I receptor antagonist, CV-11974, on ischemia and reperfusion injury of the liver."Transplantation. 71(8). 1034-1039 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogata K, Jin MB, Taniguchi M, Suzuki T, Shimamura T, Kitagawa N, Magata S, Fukai M, Ishikawa H, Ono T, Furukawa H, Fujita M, Todo S: "Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type phospholipase A_2 with LY329722."Transplantation. 71(8). 1040-1046 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishikawa H, Jin MB, Ogata T, Taniguchi M, Suzuki T, Shimamura T, Magata S, Horiuchi H, Ogata K, Masuko H, Fujita M, Furukawa H, Todo S: "Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers"Transplantation. 73(7). 1041-1048 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda T, Jin MB, Fujita M, Sakurai T, Nakayama M, Taniguchi M, Suzuki T, Shimamura T, Furukawa H, Todo S.: "A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats"Surgery. 133. 197-206 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin MB, et al.: "Liver preservation an ischemia-reperfusion injury in cadaveric liver transplantation."Clinical J.Surgery (in Japanese). 66. 148-154 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin MB, et al.: "Clinical path in liver transplantation"Clinical Surgery (in Japanese). 58(11). 144-150 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin MB: "Manual for organ transplantation in animal experiment"Nihonigakukan, Tokyo. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Keisa Takeda: "A NOVEL INHIBITOR OF RHO-ASSOCIATED PROTEIN KINASE, Y-27632, AMELIORATES HEPATIC ISCHEMIA AND REPERFUSION INJURY IN RATS"Surgery. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] MB Jin: "The role of endothelin-1 in hepatic ischemia and reperfusion injury"Journal of Gastroenterilogy. 37(9). 763-765 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taniguchi M.: "Effect of diprydamole on ischemia and reperfusion injury of canine liver"Transplantation Proceedings. 33(1-2). 933 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishikawa H.: "Elevation of cyclic nucleotides attenuates ischemia and reperfusion injury of liver"Transplantation Proceedings. 33(1-2). 982-983 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishikawa H.: "Role of cyclic nucleotides in ischemia and reperfusion injury in canine livers"Transplantation. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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