Project/Area Number |
04454329
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Digestive surgery
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Research Institution | MIE University |
Principal Investigator |
MIZUMOTO Ryuji Mie University, Faculty of Medicine, Professor, 医学部, 教授 (00025561)
|
Co-Investigator(Kenkyū-buntansha) |
OGURA Yoshifumi Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (00126963)
NOGUCHI Takashi Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40144258)
KAWARADA Yoshifumi Mie University, College of Medical Sciences, Professor, 医療技術短期大学部, 教授 (40024814)
|
Project Period (FY) |
1992 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥6,400,000 (Direct Cost: ¥6,400,000)
|
Keywords | Ischemia-reperfusion injury / Obstructive jaundice / 40% hepatectomy / Free radical / Free radical scavenger / Endotoxin / Superoxide dismutase / Active bypass / 黄疸遷延 / 網内系機能 / 肝微細構造 |
Research Abstract |
Obstructive jaundice was produced in adult mongrel dogs by cholecystectomy and ligation and cutting of the distal common bile duct. The pathophysiology of ischemia-reperfusion injury on remnant liver after hepatectomy and the occlusion of hepatic blood inflow was evaluated in dogs with obstructive jaundice. 1.When 40% hepatectomy under 10-minute occlusion of both hepatic artery and portal vein was performed for dogs with obstructive jaundice at 2 weeks after ligation of the common bile duct and chole-cystectomy, the content of lipid peroxide increased significantly in the remnant liver with reduction of SOD activity, while xanthine oxidase activity did not change. The levels of endotoxin and beta-NAH in peripheral blood had significantly increased, and phagocytic index had markedly decreased after 3 hours. Survival rate at 7 days was only 23.1% and many dogs died of liver failure. 2.Effects of free radical scavengers : When Coenzyme Q_<10>(CoQ_<10>) or stirene-co-maleic acid superoxide d
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ismutase(SM-SOD) was administered before ischemia and reflow, the development of the above phenomenon in the remnant liver was prevented significantly and the survival rate at 7days was improved remarkably to 76.9% and 69.2%. The endotoxin levels in the portal venous blood were increased significantly after reflow of the hepatic blood inflow, regardless of the administration of CoQ_<10> or SM-SOD.Whereas, the levels in the peripheral blood were markedly reduced by these drugs. 3.Effects of active bypass of the portal vein to inferior vena cava : When the hepatic blood inflow was occluded for 10 minutes with active bypass of the portal vein to inferior vena cava, the levels of endotoxin in both the portal venous blood and the peripheral blood did not change, and the remnant liver injury was milder. However, when the hepatic blood inflow was occuluded for 20 minutes with active bypass, the content of lipid peroxide increased significantly in the remnant liver with reduction of SOD activity, while the levels of endotoxin in both the portal venous blood and the peripheral blood remained the same. The level beta-NAH in peripheral blood increased significantly and the phagocytic index decreased markedly after 3 hours. Survival rate at 7 days was only 33.3% and many dogs died of liver failure. Less
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