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Experimental study on effect of preconditioning to hepatic ischemia/reperfusion injury.

Research Project

Project/Area Number 11671228
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAGINO Masato  School of Medicine, Nagoya University, Associate Professor, 医学部, 講師 (20237564)

Co-Investigator(Kenkyū-buntansha) UESAKA Katsuhiko  School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (20283434)
KAMIYA Jyunichi  School of Medicine, Nagoya University, Associate Professor, 医学部, 講師 (70194975)
NIMURA Yuji  School of Medicine, Nagoya University, Professor, 医学部, 教授 (80126888)
ODA Kouji  School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (30311715)
YUASA Norihiro  School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (00303610)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsIschemia reperfusion injury / Preconditioning / Liver failure / Hypercholesterolemia / Leukocyte / Kupffer cell / Adhesion molecule / プレコンディショニング / 虚血再灌流傷害 / 肝細胞傷害 / 肝微小循環 / SWOP
Research Abstract

Our goal of this study was to examine the effect of preconditioning to hepatic ischemia/reperfusion (I/R). At first, to establish experimental model for hepatic I/R, experiments on hepatic I/R in hypercholesterolemic mice were conducted. The objective of this series was to determine whether hypercholesterolemia affects leukocyte adhesion and tissue injury after I/R in the mouse liver. The accumulation of rhodamine-6G-labelled leukocytes and number of non-perfused sinusoids (NPS) were monitored (by intravital microscopy) in liver of normal (WT) and low-density lipoprotein receptor-deficient (LDLr^<-/->) mice for 1 hr after a 30 min period of normothermic ischemia. Plasma Alanine Transaminase (ALT) level was measured as an index of liver tissue injury Microvascular leukostasis as well as increases in NPS and plasma ALT level were observed at 60 min after hepatic I/R in both WT and in LDLr^<-/-> mice ; however, these responses were greatly exaggerated in LDLr^<-/-> mice. Pretreatment of L … More DLr^<-/-> mice with gadolinium chloride, which reduces Kupffer cell function, attenuated the hepatic leukostasis, NPS and liver tissue injury elicited by I/R.Similar protection against I/R was observed in LDLr^<-/-> mice pretreated with antibodies directed against either tumor necrosis factor-α, intercellular adhesion molecule-1 (ICAM-1), or P-selectin. These findings indicate that chronic hypercholesterolemia predisposes the hepatic microvasculature to the deleterious effects of I/R.Kupffer cell activation and the leukocyte adhesion receptors ICAM-1 and P-selectin appear to contribute to the exaggerated inflammatory responses observed in the postishemic liver of LDLr^<-/-> mice. Using this established experimental model of mice liver, a small amount of endotoxin was intraperitoneally administered 24 hours prior to 1 hour hepatic ischemia in wild-type mice. Pretreatment of endotoxin attenuated microvascular leukostasis at 60 win after hepatic I/R, and preconditioning effect in mice liver was confirmed. Hereafter, we will examine the preconditioning effect by a short duration of ischemia and elucidate its mechanism. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Naoharu Mori: "Hepatic microvascular responses to ischemia-reperfusion in low-density lipoprotein receptor knockout mice"Am J Gastrointest Liver Physiol. 279. G1257-G1264 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naoharu Mori: "Hepatic microvascular response to ischemia-reperfusion in low-density lipoprotein receptor knockout mice"Am J Physiol Gastrointest Liver Physiol. 279. G1257-G1264 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naoharu Mori: "Hepatic microvascular responses to ischemia-reperfusion in low-density lipoprotein recoptor knockout mice"Am J Physiol Gastrointest Liver Physiol. 279. G1257-G1264 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagino M: "Serum alkaline phosphatase after extensive liver resection : A study in patients with biliary tract carcinoma"Heoato-Gastroenterology. 46. 766-770 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsugane K: "A possible role nuclear ceramide and sphingosine in hepatocyte apoptosis in rat liver"Journal of Hepatplogy. 31. 8-17 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayata A: "Hepatocyte growth factor concentration in rat bile is affected by hepatic resection volume and external biliary drainage"Journal of Surgical Research. 85. 71-76 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Meda A: "Interleukin 6 in bile as an indicator of liver function after hepatectomy in patients with biliary tract carcinoma"British Journal of Surgery. 86. 458-464 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurumiya Y: "Active from of human hepatocyte growth factor is excreted into bile after hepatobiliary resection"Journal of Hepatology. 30. 22-28 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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