| Project/Area Number |
14370355
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
SHIMAHARA Yasuyuki Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (30196498)
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| Co-Investigator(Kenkyū-buntansha) |
KAWADA Norifumi Oosaka City University, School of Medicine, Lecturer, 医学部, 講師 (30271191)
NAKAMURA Hajime Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (70303914)
山本 成尚 京都大学, 医学研究科, 助手 (30253298)
山岡 義生 京都大学, 医学研究科, 教授 (90089102)
寺嶋 宏明 京都大学, 医学研究科, 講師 (40314215)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥10,600,000 (Direct Cost: ¥10,600,000)
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| Keywords | hepatic stellate cell / thioredoxin / ROCK / Rho kinase inhibitor / ischemia / reperfusion injury / hepatic microcirculation / intravital microscopy / N-acetylcisteine / liver failure / Rho kinase阻害剤 / 肝繊維化 / 急性肝不全 / 肝腺維化 |
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| Research Abstract |
1)Relationship between thioredoxin and stellate cell function : Thioredoxin is a small redox-active protein with anti-oxidant and anti-apoptotic effect. We have investigated the protective effect of thioredoxin for hepatic fibrosis. Induction of endogenous thioredoxin was obvious in hepatocytes of thioacetamide-induced fibrotic liver of rats. Overexpression of thioredoxin inhibited tumor necrosis factor-(x-induced death of HepG2 cells. Thioacetamide-induced fibrosis and accumulation of malondialdehyde in the liver was suppressed in transgenic mice as compared with wild-type mice. Hepatic stellate cells isolated from transgenic mice was less proliferative than those isolated from wild type mice. Recombinant thioredoxin significantly inhibited DNA synthesis of primary-cultured stellate cells under serum or PDGF-BB stimulation. Thioredoxin failed to control collagen gene expression in cultured stellate cells. Thioredoxin has a potential to control hepatic fibrosis via inhibiting hepatocyt
… More
e death, proliferation of stellate cells and oxidative stress.
2)Hepatic microcirculation and Rock/Rho kinase inhibitor, Y-27632 : Rock/Rho kinase inhibitor, Y-27632 is also known to prevent activation of hepatic stellate cell and prevent fibrosis. We have investigated it in ischemia/reperfusion model of rat liver using hemi-lateral clamp of the liver. Y-27632 protected ischemia/reperfusion-induced injury of the liver through remarkable improvement of hepatic microcirculation, which was observed by intravital microscopy. Diameter of sinusoid and postsinusoidal venule, sinusoidal perfusion rate were maintained as compared to sham group. Adherence of leucocytes in the sinusoid and postsinusoidal venule was much less, which results also in protection of disturbance of the blood flow. Y-27632 also exhibited to improve disturbance of microcirculation due to endotoxemia.
3)Effect of NAC (N-acetylcisteine) on clinical postoperative liver failure : NAC (N-acetylcisteine) was administered to a posthepatectomized patient with hyperbilirubinemia. Serum bilirubin level tended to decreased after enteral administration of NAC. Less
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