| Project/Area Number |
05454248
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
ISHII Hiromasa Keio University, Dept of Internal Medicine, Professor, 医学部, 教授 (20051500)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYA Susumu Keio University, Dept of Intern Med, Instructor, 医学部(消化器内科), 助手 (10220089)
HORIE Yoshie Keio University, Dept of Intern Med, Instructor, 医学部(消化器内科), 助手 (70229227)
YOKOYAMA Akira Keio University, Depat of Intern Med, Instructor, 医学部(消化器内科), 助手 (50200910)
KATO Shinzo Keio University, Dept of Intern Med, Associate Profess, 医学部(消化器内科), 講師 (30177448)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | microcirculatory disturbance / oxidative stress / liver injury / prostagrandin / endotoxin / nitric oxide / alcohol / ブロスタグランディン |
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| Research Abstract |
Pathogenetical role of oxidative stress and microcirculatory disturbances were investigated by experimental model in vivo and in perfused rat liver. To that effect, intravital fluorescence microscopy assisted by ultrasensitive camera and various fluorescence probes were used. Ischemica reperfusion injury was demonstrated to star from midzone of the hepatic lobule and extended to pericentral area. This was inhibited by xanthine oxidase inhibitor and prostagrandin E1. Microcirculatory disturbances in acute ethanol intoxication was demonstrated with fluorescence labeled RBC,at high ethanol concentration but not at low ethanol concentration. Increase of hepatic NADH in centrilobular area was also demonstrated in vivo as well as perfused liver. Endotoxin induced liver injury was demonstrated to be mediated by mitochondrial dysfunction by the release of nitric oxide from Kupffer cell. This was blocked by NO inhibitor such as L-NMMA and i-NOS inhibitor. In these experimental hepatic injury, oxidative stress and microcirculatory disturbances playd an important role in pathogenesis.
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