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2001 Fiscal Year Final Research Report Summary

Strategy for Liver Failure by Regulating Hepatic Microcirculation through Hepatic Stellate Cell Activatity

Research Project

Project/Area Number 12470238
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SHIMAHARA Yasuyuki  Kyoto University, Medicine, Associate Professor, 医学研究科, 助教授 (30196498)

Co-Investigator(Kenkyū-buntansha) TERAJIMA Hiroaki  Kyoto University, Medicine, Lecturer, 医学研究科, 講師 (40314215)
YAMAMOTO Naritaka  Kyoto University, Medicine, Associate Professor, 医学研究科, 助手 (30253298)
YAMAOKA Yoshio  Kyoto University, Medicine, Associate Professor (Chairman), 医学研究科, 教授 (90089102)
KAWADA Norihumi  Osaka City University, Medicine, Lecturer, 医学部, 講師 (30271191)
Project Period (FY) 2000 – 2001
Keywordshepatic stellate cell / hepatic microcirculation / Liver failure / Intravital microscopyu / Liver fibrosis / ROCK / Rho kinase inhibitor / Y-27632 / enndotoxin
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 series of the 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 hemHateral 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.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Shimahara-Y: "Significance of serum type IV collagen level of hepatectomized patients with chronic liver damage"World-J-Surg. 26(4). 451-456 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uyama-N: "Regulation of Cultured Rat Hepatocyte Proliferation by Stellate Cells"Journal of Hepatology. 36. 590-599 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawada, -N: "Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells"J-Biol-Chem.. 276(27). 25318-25323 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuyama-H: "Regulation of cell growth by redo-mediated extracellular proteolysis of platelet-derived growth factor receptor beta."J Biol Chem. 276(30). 28274-28280 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuyama-H: "N-acetyl cystelne Inhibits PDGF-dependent proliferation of primary cultured o rat hepatic stellate cells through degradation of PDGF receptor and attenuates progress of liver fibrosis in rat models"Cells of Hepatic Sinusoid. 8. 274-276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uyama-N: "The interaction between hepatocytes and stellate cells on individual cell proliferation and differentiation"Cells of Hepatic Sinusoid. 8. 51-54 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimahara-Y, Yamamoto-N, Uyama-N, et al.: "Significance of serum type IV collagen level of hepatectomized patients with chronic liver damage"World J Surg. 26(4). 451-456 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uyama-N, Shimahara-Y, Kawada-N, Seki-S, Okuyama-H, Iimuro-Y, Yamaoka-Y: "Regulation of Cultured Rat Hepatocyte Proliferation by Stellate Cells"Journal of Hepatology. 36. 590-599 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawada-N, Kristensen-D-B, Asahina-K, Nakatani-K, Minamiyama-Y, Seki-S, Yoshizato-K: "Characterization of a stellate cell activation-associated proten (STAP) with peroxidase activity found in rat hepatic stellate cells"J-Biol-Chem.. 276(27). 25318-23 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuyama-H, Shimahara-Y, Kawada-N, Seki-S, Kristensen-D-B, Yoshizato-K, Uyama-N, Yamaoka-Y: "Regulation of cell growth by redox-mediated extracellular proteolysis of platelet-derived growth factor receptor beta"J-Biol-Chem.. 276(30). 28274-80 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuyama-H, Kawada-N, Shimahara-Y, Uyama-N, Yamaoka-Y: "N-acetyl cysteine inhibits PDGF-dependent proliferation of primary cultured o rat hepatic stellate cells through degradation of PDGF receptor and attenuates progress of liver fibrosis in rat models"Cells of Hepatic Sinusoid. 8. 274-276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uyama-N, Kawada-N, Ikuyama-H, Iimuro-Y, Kaneda-K, Shimahara-Y, Yamaoka-Y: "The interaction between hepatocytes and stellate cells on individual cell proliferation and differentiation"Cells of Hepatic Sinusoid. 8. 51-54 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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