Activated leukocytes play an important role in ischemia/reperfusion (I/R)-induced liver injury. Proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin (IL)-l, are implicated in this condition. Since plasminogen activator inhibitor (PAI)-1 is implicated in disseminated intravascular coagulation associated with sepsis in which such cytokines play an important role, it is possible that PAI-1 is critically involved in I/R-induced liver injury. In the present study, we examined this possibility using animal model of I/R-induced liver injury. Hepatic damage was induced by 60, 90, or 120 min-ischemia and the subsequent reperfusion. The coagulation abnormalities was evaluated by measuring plasma fibrinogen concentration and serum concentration of fragment E of fibrin and fibrinogen degradation products [FDP (E)]. Serum concentration of TNF was measured by ELISA method. Plasma concentration of PAI-1 was measured by chromogenic assay kit. Serum levels of TNF and PAI-1 were elevated with the increase in ischémie period (from 60 to 120 min) of the rat liver in animals subjected to hepatic 1/R. These levels well correlated with the extent of coagulation abnormalities in animals subjected to hepatic I/R. The elevation of transaminases levels and coagulation abnormalities were significantly inhibited by DEGR-Xa, a selective inhibitor of thrombin generation, in animals subjected to 120 min I/R. Leukocyte depletion markedly inhibited the increase in transaminases levels and coagulation abnormalities as well as the increase in the plasma levels of both TNF and PAI-1 in rats subjected to 120 min I/R. These results suggest that PAI-1 is critically involved in I/R-induced liver injury by inducing microthrombus formation when the ischemia is prolonged. Furthermore, the elevation of PAI-1 may deeply be related to the action of TNF.
|Number of pages||1|
|Journal||Fibrinolysis and Proteolysis|
|Issue number||SUPPL. 1|
|Publication status||Published - 1998 Dec 1|
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