Hypoxia inducible factor-1αaccumulation in steatotic liver preservation:Role of nitric oxide  

作　　者：Mohamed Amine Zaouali Ismail Ben Mosbah Eleonora Boncompagni Hassen Ben Abdennebi Maria Teresa Mitjavila Ramon Bartrons Isabel Freitas Antoni Rimola Joan Roselló-Catafau 

机构地区：[1]Experimental Hepatic Ischemia Reperfusion Unit, Institut of Biomedical Research of Barcelona,Spanish National Research Council,08036,Barcelona,Spain [2]Liver Transplantation and Graft Viability Unit,August Pi i Sunyer Biomedical Research Institut,08036,Barcelona, Spain [3]Animal Biology Department,Pavia University,27100,Pavia,Italy [4]Laboratory of Human Physiology, Faculty of Pharmacy,University of Monastir,5000,Monastir, Tunisia [5]Department of Physiology,Faculty of Biology,University of Barcelona,08028,Barcelona,Spain [6]Physiological Sciences Department,Bellvitge Campus,Institut of Biomedical Research of Bellvitge-Barcelona University,08907,Barcelona,Spain

出　　处：《World Journal of Gastroenterology》2010年第28期3499-3509,共11页世界胃肠病学杂志（英文版）

基　　金：Supported by The Ministerio de de Sanidad y Consumo(PI081988);CIBER-EHD,Instituto Carlos Ⅲ,Madrid and Ministerio de Asuntos Exteriores y de Cooperación Internacionales(A/020255/08 and A/02987/09),Madrid

摘　　要：AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model and we evaluated HIF-1αin steatotic and non-steatotic livers preserved for 24 h at 4℃in University of Wisconsin and IGL-1 solutions,and then subjected to 2 h of normothermic reperfusion.After normoxic reperfusion,liver enzymes,bile production,bromosulfophthalein clearance,as well as HIF-1αand NO[endothelial NO synthase(eNOS)activity and nitrites/nitrates]were also measured.Other factors associated with the higher susceptibility of steatotic livers to IRI,such as mitochondrial damage and vascular resistance were evaluated. RESULTS:A significant increase in HIF-1αwas found in steatotic and non-steatotic livers preserved in IGL-1 after cold storage.Livers preserved in IGL-1 showed a significant attenuation of liver injury and improvement in liver function parameters.These benefits were enhanced by the addition of trimetazidine(an antiischemic drug),which induces NO and eNOS activation, to IGL-1 solution.In normoxic reperfusion,the presence of NO favors HIF-1αaccumulation,promoting also the activation of other cytoprotective genes,such as hemeoxygenase-1. CONCLUSION:We found evidence for the role of the HIF-1α/NO system in fatty liver preservation,especially when IGL-1 solution is used.AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model and we evaluated HIF-1αin steatotic and non-steatotic livers preserved for 24 h at 4℃in University of Wisconsin and IGL-1 solutions,and then subjected to 2 h of normothermic reperfusion.After normoxic reperfusion,liver enzymes,bile production,bromosulfophthalein clearance,as well as HIF-1αand NO[endothelial NO synthase(eNOS)activity and nitrites/nitrates]were also measured.Other factors associated with the higher susceptibility of steatotic livers to IRI,such as mitochondrial damage and vascular resistance were evaluated. RESULTS:A significant increase in HIF-1αwas found in steatotic and non-steatotic livers preserved in IGL-1 after cold storage.Livers preserved in IGL-1 showed a significant attenuation of liver injury and improvement in liver function parameters.These benefits were enhanced by the addition of trimetazidine(an antiischemic drug),which induces NO and eNOS activation, to IGL-1 solution.In normoxic reperfusion,the presence of NO favors HIF-1αaccumulation,promoting also the activation of other cytoprotective genes,such as hemeoxygenase-1. CONCLUSION:We found evidence for the role of the HIF-1α/NO system in fatty liver preservation,especially when IGL-1 solution is used.

关 键 词：Fatty liver Tissue preservation Hypoxia inducible factor-1α IGL-1 Nitric oxide TRIMETAZIDINE 

分 类 号：R575.5[医药卫生—消化系统]