| Project/Area Number |
13557100
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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 | 展開研究 |
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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, Medicine, Associate Professor, 医学研究科, 助教授 (30196498)
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| Co-Investigator(Kenkyū-buntansha) |
KAWADA Norihumi Osaka City University, Medicine, Lecturer, 医学研究科, 講師 (30271191)
YAMAOKA Yoshio Kyoto University, Medicine, Professor(Chairman), 医学研究科, 教授 (90089102)
YAMAMOTO Naritaka Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (30253298)
TERAJIMA Hiroaki Kyoto University, Medicine, Lecturer, 医学研究科, 講師 (40314215)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2002: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2001: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | hepatic stellate cell / hepatic microcirculation / Liver failure / Intravital microscopyu / Liver fibrosis / ROCK / Rho kinase inhibitor / Y-27632 / enndotoxin / 肝障害 / 虚血再潅流障害 |
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| Research Abstract |
Hepatic stellate cell. is known to regulate hepatic sinusoidal blood flow through its contraction and relaxation. When it is contracted by activation, sinusoidal blood flow is reduced. Therefore, it is considered that regulation of activation of hepatic stellate cell can be a potential strategy to improve hepatic microcirculation. We have clarified in TAA-induced cirrhosis model of rats that N-acetyl-L-cysteine (NAC) has a powerful effect on prevention of hepatic stellate cell activation and progress of fibrosis. In such model, microcirculation was well maintained. Rock/Rho kinase inhibitor, Y-27632 is also known to prevent activation of hepatic stellate cell and prevent fibrosis. In this study, we have examined whether Y-27632 has an effect on improvement of hepatic microcirculation. 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. Diamiter 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. Tioredoxin has an effect of antioxidant like NAC. We clarified that thioredoxin prevents hepatic fibrosis in the chronic liver injury model and also protect hepatic cell death in acute hepatitis model.
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