Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcome...Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcomes.The underlying cellular and molecular reactions are extremely complex and not completely understood.Anaerobic metabolism,ATP depletion,intracellular acidosis,calcium overload,mitochondrial dysfunction,oxidative stress,activation of Kupffer cells and neutrophils,platelet aggregation,nitric oxide production,activation of the complement system and overexpression of cytokines and chemokines constitute the main pathophysiological actions and pathways for possible therapeutic strategies.Prostaglandins(PGs)are a group of biologically active lipid compounds called eicosanoids with many physiological activities.Prostacyclin(PGI_(2))is a member of the PGs family with an unstable chemical structure and a very short half-life.PGI_(2)has potent vasodilating activity,inhibits platelet activation and exerts anti-inflammatory effects.PGI_(2)has been evaluated in chronic liver disease as a mediator of hepatic stellate cell function,an antiproliferative and antifibrotic agent and a regulator of the hepatic microcirculation.In recent decades,the cytoprotective effects of PGI_(2)analogs on hepatic ischemiareperfusion injury have been experimentally and clinically studied.Moreover,the administration of synthetic PGI_(2)analogs to patients who underwent liver transplantation produced very encouraging results.The downregulation of PGE_(2) production,reduction of neutrophil aggregation in liver lobules,regulation of local microcirculatory homeostasis,improvement in mitochondrial function,alleviation of hepatic oxidative stress,suppression of the c-Jun N-terminal kinase and p38 cascades and downregulation of tumor necrosis factor-alpha and interleukin-1βproduction constitute some of the underlying physiological mechanisms of the beneficial effects of PGI_(2)on hepatic ischemia-reperfusion injury.Thus,PGI_(2)analogs appear to hold great promise for the management of hepatic ischemia-reperfusion injury,but further research is needed.展开更多
文摘Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcomes.The underlying cellular and molecular reactions are extremely complex and not completely understood.Anaerobic metabolism,ATP depletion,intracellular acidosis,calcium overload,mitochondrial dysfunction,oxidative stress,activation of Kupffer cells and neutrophils,platelet aggregation,nitric oxide production,activation of the complement system and overexpression of cytokines and chemokines constitute the main pathophysiological actions and pathways for possible therapeutic strategies.Prostaglandins(PGs)are a group of biologically active lipid compounds called eicosanoids with many physiological activities.Prostacyclin(PGI_(2))is a member of the PGs family with an unstable chemical structure and a very short half-life.PGI_(2)has potent vasodilating activity,inhibits platelet activation and exerts anti-inflammatory effects.PGI_(2)has been evaluated in chronic liver disease as a mediator of hepatic stellate cell function,an antiproliferative and antifibrotic agent and a regulator of the hepatic microcirculation.In recent decades,the cytoprotective effects of PGI_(2)analogs on hepatic ischemiareperfusion injury have been experimentally and clinically studied.Moreover,the administration of synthetic PGI_(2)analogs to patients who underwent liver transplantation produced very encouraging results.The downregulation of PGE_(2) production,reduction of neutrophil aggregation in liver lobules,regulation of local microcirculatory homeostasis,improvement in mitochondrial function,alleviation of hepatic oxidative stress,suppression of the c-Jun N-terminal kinase and p38 cascades and downregulation of tumor necrosis factor-alpha and interleukin-1βproduction constitute some of the underlying physiological mechanisms of the beneficial effects of PGI_(2)on hepatic ischemia-reperfusion injury.Thus,PGI_(2)analogs appear to hold great promise for the management of hepatic ischemia-reperfusion injury,but further research is needed.
