Role of p38 MAPK pathway in 17beta-estradiol-mediated attenuation of hemorrhagic shock-induced hepatic injury

摘要

A growing body of evidence indicates that hormonal mechanisms are involved in regulating posttraumatic organ injury (5, 6, 13, 32). Clinical and experimental studies suggest that females tolerate injury better than males (4). In this regard, we have found that hepatic injury is significant in male animals and ovariectomized females but not in proestrus females, a state with the highest plasma levels of E2 following hemorrhagic shock and fluid resuscitation (9, 15, 31). Studies also show that resistance of proestrus female rats to gut injury and gut-induced distant organ injury is greater than that observed in male rats (3). In this study, we hypothesize that the E2-mediated attenuation of liver injury following hemorrhagic shock occurs via the p38 MAPK-dependent HO-1 pathway. To test this, male rats were treated with E2 alone and in combination with the p38 MAPK inhibitor SB-203580 following hemorrhagic shock. The effects of these treatments were then examined on serum alanine aminotransferase (ALT) and asparate aminotransferase (AST) as well as hepatic tissue myeloperoxidase (MPO) activity, p38 MAPK, HO-1, cleaved caspase-3, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant (CINC)-l, and CINC-3 levels following trauma-hemorrhagic shock.