1996 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その治療方法についての検討

Research Project

Project/Area Number	07671424
Research Category	Grant-in-Aid for Scientific Research (C)
Research Institution	Showa University
Principal Investigator	中野浩昭和大学, 医学部, 助手 (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, 講師 (10255797)
Keywords	閉塞性黄疸ラット / 還元型グルタチオン / 酸化型グルタチオン / hepatocellular oxidative stress / neutrophil oxidative stress / N-acetylcysteine
Research Abstract	膵胆道系悪性腫瘍に伴う閉塞性黄疸の病態解明と治療法の研究を目的として,閉塞性黄疸の病態と活性酸素障害との関連性を検討した.[方法]ウイスター系雄性ラットの総胆管結紮により,1週間と2週間の閉塞性黄疸モデルを作成した.実験1として,sham群,1週間閉塞性黄疸群,2週間閉塞性黄疸群を作成した.実験2として,2週間閉塞性黄疸ラットに5%Glucose 1ml連日皮下注した群(D5%群)とN-acetylcysteine 150mg/kg1ml連日皮下注した群(NAC群)を比較した.測定項目として,好中球の活性酸素産生能をflow cytometryで測定した(DCF-index).また,肝細胞oxidative stressは,HPLCにより肝組織内の還元型グルタチオン(GSH)と酸化型グルタチオン(GSSG)を同時測定して,GSSG/GSH値で検討した.[結果]実験1.Hepatocellular oxidative stressの指標である肝組織GSSG/GSHは,Sham群に比較して,2週間群にて有意に高値であった.末梢血中における好中球oxidative stress(DCF-index)は,2週間群はsham群,1週間群に比し,有意に高値となった(p<0.01).肝組織内浸潤好中球oxidative stressは,2週群はSham群に比し,有意に高値となった(p<0.05).実験2.NAC投与群はD5%群に比してGOT値の改善が認められた.Hepatocellular oxidative stressの指標であるGSSG/GSHはNAC投与により低下した。NACの投与により門脈血流量、肝組織血流量の有意な上昇を認めた.しかしかながら,好中球oxidative stressは,末梢血,肝組織中も,NAC投与で上昇を認めた.[結論]Free radical scavengerであるNACを投与すると,肝機能,hepatocellular oxidative stressが改善されるが,好中球oxidative stressは上昇した.閉塞性黄疸の肝機能障害にhepatocellular oxidative stressが関与し,oxidative stressの治療は効果的である可能性が示唆された.しかし,好中球oxidative stressの抑制は,治療効果につながらない可能性が示唆された.

Research Products

(10 results)

All Other

All Publications (10 results)

[Publications] Nakano H,et al.: "Amelioration of hepatocellular integnity and inhibition of sinusoidal oxidative stress by N-acctylcysteine pretreatment in cold ischemia-reperfusion injury of rat liver." Eur Surg Res. 28. 245-255 (1996)
[Publications] Nakano H,et al.: "Histopathological response to preperative chemotherapy induding 5-flurouracil additionally assessed by immunocytochemical and pharmacologic parameters in advanced gastric cancer patients." Surg Today. 26. 482-488 (1996)
[Publications] Nakano H,et al.: "The effects of NAC or 1A29 on ischemia-reperfusion injury of the rat steatotic liver." Eur Surg Res. suppl1. 16-17 (1996)
[Publications] Nakano H,et al.: "Prediction of postoperative decompensated lvier function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicated with chronic liver diseases." Br J Surg in press.
[Publications] Nakano H,et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury." Eur Surg Res. 29. 93-100 (1997)
[Publications] Nakano H,et al.: "Hepanin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-scdivated human vascular endothelial cells under nonstatic conditions." Eur Surg Res. 28. 428-435 (1996)
[Publications] Nakano H,et al.: "Prognostic evaluation of locally advanced gastric cancee patients with preoperative downstaging chemotherapy." Cancer Detect Prev.20. 447-448 (1996)
[Publications] Nakano H,et al.: "The effects of N-acetylcysteine or anti-ICAM-1 monoclonal antibody against ischemia-repefusion injury of the rat steatotic liver produced by choline-methionine deficient diet." Hepatology in press.
[Publications] Nakano H,et al.: "The effecacy of N-acetylcysteine preconditioning against reperfusion injury after prolonged cold ischemia in a severely glutathione-decreased rat liver produced by buthionine sulfoximine.Eur J Surg in press." Eur J Surg in press.
[Publications] Nakano H,et al.: "Prognosis of HCC with chronic liver diseases and risk of hepatectomy:Prediction using technetium 99m-GSA liver scintigraphy." xxx World Congress of the International College of Surgeous.Monduzzi EditoreS.p.A.771-774 (1996)

1996 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その治療方法についての検討

Principal Investigator

中野 浩 昭和大学, 医学部, 助手 (10241035)

Research Products

[Publications] Nakano H,et al.: "Amelioration of hepatocellular integnity and inhibition of sinusoidal oxidative stress by N-acctylcysteine pretreatment in cold ischemia-reperfusion injury of rat liver." Eur Surg Res. 28. 245-255 (1996)

[Publications] Nakano H,et al.: "Histopathological response to preperative chemotherapy induding 5-flurouracil additionally assessed by immunocytochemical and pharmacologic parameters in advanced gastric cancer patients." Surg Today. 26. 482-488 (1996)

[Publications] Nakano H,et al.: "The effects of NAC or 1A29 on ischemia-reperfusion injury of the rat steatotic liver." Eur Surg Res. suppl1. 16-17 (1996)

[Publications] Nakano H,et al.: "Prediction of postoperative decompensated lvier function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicated with chronic liver diseases." Br J Surg in press.

[Publications] Nakano H,et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury." Eur Surg Res. 29. 93-100 (1997)

[Publications] Nakano H,et al.: "Hepanin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-scdivated human vascular endothelial cells under nonstatic conditions." Eur Surg Res. 28. 428-435 (1996)

[Publications] Nakano H,et al.: "Prognostic evaluation of locally advanced gastric cancee patients with preoperative downstaging chemotherapy." Cancer Detect Prev.20. 447-448 (1996)

[Publications] Nakano H,et al.: "The effects of N-acetylcysteine or anti-ICAM-1 monoclonal antibody against ischemia-repefusion injury of the rat steatotic liver produced by choline-methionine deficient diet." Hepatology in press.

[Publications] Nakano H,et al.: "The effecacy of N-acetylcysteine preconditioning against reperfusion injury after prolonged cold ischemia in a severely glutathione-decreased rat liver produced by buthionine sulfoximine.Eur J Surg in press." Eur J Surg in press.

[Publications] Nakano H,et al.: "Prognosis of HCC with chronic liver diseases and risk of hepatectomy:Prediction using technetium 99m-GSA liver scintigraphy." xxx World Congress of the International College of Surgeous.Monduzzi EditoreS.p.A.771-774 (1996)

中野浩昭和大学, 医学部, 助手 (10241035)