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Investigation for gene transfer regulation of organ failure induced by hepatic ischemia/reperfusion injury

Research Project

Project/Area Number 17591371
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionChiba University

Principal Investigator

YOSHIDOME Hiroyuki  Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 講師 (10312935)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Masaru  Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (70166156)
KIMURA Fumio  Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 助教授 (70334208)
KATO Atsushi  Chiba University, Graduate School of Medicine, Assistant Professor, 医学部附属病院, 助手 (70344984)
YOSHITOMI Hideyuki  Chiba University, Graduate School of Medicine, Assistant Professor, 医学部附属病院, 助手 (60375631)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsischemia and reperfusion injury / transcriptional factor / infection / organ failure / cytokine / chemokine / sepsis / apoptosis / 阻血 / 再灌流 / 障害肝
Research Abstract

Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation. One possible cause is hepatic ischemia/reperfusion. The aim of the current study was to determine the role for NOS isoform expression and apoptosis in steatotic liver ischemia/reperfusion injury. Using a murine model of partial hepatic ischemia, expression of NOS isoforms, apoptosis, transcriptional activation, serum ALT levels, and histology were examined. Although serum ALT levels were elevated and histology revealed severe liver injury in terms of steatosis relative to normal liver, steatotic ischemia/reperfusion injury was independent of neutrophil-mediated injury. In steatotic liver, an increase in iNOS expression but little upregulation of eNOS was evident and hepatic apoptosis defined by TUNEL staining was significantly induced which was associated with upregulation of cleaved caspases 9 and 3, but not caspase 8 compared with normal liver. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum ALT levels and apoptosis were greatly reduced, but treated with L-NAME, serum ALT levels were greatly upregulated in the steatosis compared with normal liver. Our data suggested that steatotic liver is vulnerable to ischemia/reperfusion which may be caused by different expression pattern of NOS isoforms and susceptibility to apoptosis by mitochondrial permeability transition.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 Other

All Journal Article (14 results)

  • [Journal Article] Renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery.2006

    • Author(s)
      Suzuki T, Yoshidome H, Kimura F, Kato A, Miyazaki M, et al.
    • Journal Title

      Journal of the American College of Surgeon 202

      Pages: 87-92

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection.2006

    • Author(s)
      Kimura F, Yoshidome H, Kato A, Miyazaki M, et al.
    • Journal Title

      Journal of Surgical Research 133

      Pages: 102-112

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy.2006

    • Author(s)
      Makino H, Shimizu H, Ito H, Kimura F, Ambiru S, Togawa A, Ohtsuka M, Yoshidome H, Kato A, Yoshitomi H, Sawada S, Miyazaki M.
    • Journal Title

      World Journal of Gastroenterology 12

      Pages: 2053-2059

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection.2006

    • Author(s)
      Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Nozawa S, Furukawa K, Mitsuhashi N, Sawada S, Takeuchi D, Ambiru S, Miyazaki M.
    • Journal Title

      Journal of Surgical Research 133

      Pages: 102-112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery.2006

    • Author(s)
      Suzuki T, Yoshidome H, Kimura F, Kato A, Miyazaki M, et al.
    • Journal Title

      Journal of the American College of Surgeon 202・1

      Pages: 87-92

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased plasma levels of IL-6 and IL-8 are associated with surgical site infection after pancreaticoduodenectomy.2006

    • Author(s)
      Kimura F, Yoshidome H, Kato A, Miyazaki M, et al.
    • Journal Title

      Pancreas 32・2

      Pages: 178-185

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed regeneration after partial hepatectomy.2006

    • Author(s)
      Makino H, Shimizu H, Kimura F, Yoshidome H, Kato A, Miyazaki M, et al.
    • Journal Title

      World Journal of Gastroenterology 12・13

      Pages: 2053-2059

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Should the inferior vena cava be reconstructed after resection for malignant tumors?2005

    • Author(s)
      Yoshidome H, Kimura F, Kato A, Miyazaki M, et al.
    • Journal Title

      American Journal of Surgery 189

      Pages: 419-424

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplantation.2005

    • Author(s)
      Shimizu H, Kimura F, Yoshidome H, Kato A, Miyazaki M, et al.
    • Journal Title

      Hepatogastroenterology 52

      Pages: 1172-1175

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 肝阻血再灌流障害におけるシグナル伝達機構-up-to-date2005

    • Author(s)
      吉留博之, 加藤 厚, 木村文夫, 宮崎 勝他
    • Journal Title

      外科と代謝・栄養 39

      Pages: 113-120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats.2005

    • Author(s)
      Shimizu H, Kimura F, Yoshidome H, Kato A, Miyazaki M, et al.
    • Journal Title

      World Journal of Gastroenterology 11・46

      Pages: 7254-7760

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats.2005

    • Author(s)
      Shimizu H, Mitsuhashi N, Ohtsuka M, Ito H, Kimura F, Ambiru S, Togawa A, Yoshidome H, Kato A, Miyazaki M.
    • Journal Title

      World Journal of Gastroenterology 11

      Pages: 7254-7260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 肝阻血再灌流障害におけるシグナル伝達機構-up-to-date2005

    • Author(s)
      吉留博之, 加藤 厚, 木村文夫, 宮崎勝他
    • Journal Title

      外科と代謝・栄養 39

      Pages: 113-120

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery.

    • Author(s)
      Suzuki T, Yoshidome H, Kimura F, Kato A, Miyazaki M, et al.
    • Journal Title

      Journal of the American College of Surgeon (in press)

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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