1997 Fiscal Year Annual Research Report

閉塞性黄疸外科的侵襲時の肝内活性酸素産生の病態解析と治療方法についての検討

Research Project

Project/Area Number	07671424
Research Institution	Showa University
Principal Investigator	中野浩昭和大学, 医学部, 講師 (10241035)
Co-Investigator(Kenkyū-buntansha)	熊田馨昭和大学, 医学部, 教授 (00025602) 緑川武正昭和大学, 医学部, 助教授 (10255797)
Keywords	閉塞性黄疸 / endotoxin shock / N-acetylcysteine / α-glutathione-S-transferase / mitochondrial GSSG / GSH / 好中球活性酸素産生 / 肝microcirculatory flow
Research Abstract	本研究は,閉塞性黄疸下にある動物において外科的侵襲を加えた場合に,その侵襲後の病態に,いかに活性酸素産生が関与しているか,また,その病態改善の治療方法を検討することを目的としている. ラットの肝外胆管を結紮して,2週間後に採血し,中等度の閉塞性黄疸を作成することに成功した.この閉塞性黄疸ラットモデルを使用して,無治療群(5%glucose 2週間投与群)とN-acetylcysteine(NAC)2週間投与群とを作成し,Endotoxinを投与するモデルを作成した.NAC群は5%glucose群に比して,肝障害(血清α-glutathione-S-transferase濃度)が軽度で,endotoxinショック時の肝細胞障害が軽度であった.肝細胞質のoxidative stressの指標である還元型グルタチオン(GSSG)と酸化型グルタチオン(GSH)の比は,有意にNAC群で低値で,肝ミトコンドリアのoxidative stressの指標であるmitochondrial GSSG/GSH値は,有意にNAC群で低値であった.また,肝ATP値は有意にNAC群で低値で,肝内に侵潤した好中球活性酸素産生を抑制する効果が認められた.以上より,本モデルにおけるNACの肝細胞機能保持効果が明らかとなった. また,閉塞性黄疸犬のendotoxin投与モデルにおいて,NACは,門脈血流増加作用,肝microcirculatory flow増加効果,肝ATP増加効果,肝ミトコンドリアGSH増加効果が証明された.以上より,閉塞性黄疸endotoxin shockモデルにおけるNACの有用性が証明された.

Research Products
(5 results)

All Other

All Publications (5 results)

[Publications] Nakano H, et al.: "The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by choline-methionine deficient diet." Hepatology. 26. 670-678 (1997)
[Publications] Nakano H, et al.: "Prediction of postoperative decompensated liver function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicated with chronic liver diseases." British Journal of Surgery. 84. 793-796 (1997)
[Publications] Nakano H, et al: "Augmentation of mitochondrial glutathione by S-adenosyl-L-methionine in ischemia-reperfusion injury of the rat steatotic liver induced by choline-methionine deficient diet." European Surgical Research. 30. 34-42 (1998)
[Publications] Nakano H, et al.: "Predicting Survival and Postoperative Complications with Tc-GSA Liver Scintigraphy in Hepatocellular Carcinoma." Hepato-gastroenterology. (in press.).
[Publications] Nakano H, et al: "Allopurinol reduced hepatic ischemia-reperfusion injury exacerbated by inhalation of high-concentration oxygen in rats." European Surgical Research. 29. 429-437 (1997)

1997 Fiscal Year Annual Research Report

閉塞性黄疸外科的侵襲時の肝内活性酸素産生の病態解析と治療方法についての検討

Principal Investigator

中野 浩 昭和大学, 医学部, 講師 (10241035)

Research Products

[Publications] Nakano H, et al.: "The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by choline-methionine deficient diet." Hepatology. 26. 670-678 (1997)

[Publications] Nakano H, et al.: "Prediction of postoperative decompensated liver function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicated with chronic liver diseases." British Journal of Surgery. 84. 793-796 (1997)

[Publications] Nakano H, et al: "Augmentation of mitochondrial glutathione by S-adenosyl-L-methionine in ischemia-reperfusion injury of the rat steatotic liver induced by choline-methionine deficient diet." European Surgical Research. 30. 34-42 (1998)

[Publications] Nakano H, et al.: "Predicting Survival and Postoperative Complications with Tc-GSA Liver Scintigraphy in Hepatocellular Carcinoma." Hepato-gastroenterology. (in press.).

[Publications] Nakano H, et al: "Allopurinol reduced hepatic ischemia-reperfusion injury exacerbated by inhalation of high-concentration oxygen in rats." European Surgical Research. 29. 429-437 (1997)

中野浩昭和大学, 医学部, 講師 (10241035)