A nem szerepe traumat es verveszteses sokkot kovetoen.

摘要

Despite significant advances in the management of trauma victims, sepsis and the ensuing multiple organ failure (MOF) continue to be the most common cause of mortality in surgical intensive care units. Several clinical and experimental studies suggest that gender affects the immune and organ functions under physiologic and pathophysiologic conditions. Although a huge amount of information is available on these gender dimorphic observations, the underlying mechanisms are less known. In our experiments we examined the effect of gender on neutrophil function, on heme oxygenase activity and on liver function following trauma (T) and hemorrhagic shock (H). To study this, proestrus female and male Sprague-Dawley rats underwent a 5 cm midline laparotomy (i.e., induction of a soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mmHg for ∼90 min, after which they were resuscitated with Ringer's lactate solution (4x the shed blood volume). Circulating polymorphonuclear granulocytes (PMNs) were assessed for superoxide (O2- ) and elastase production and different tissue samples were analyzed for myeloperoxidase (MPO) activity and TBARS (thiobarbituric acid reactive substances) as a marker of oxidative injury, at 2 and 24 hr after resuscitation. Liver samples were also collected for analysis of heme oxygenase expression and activity, while peripheral plasma samples were collected and alanine aminotransferase (ALT) levels were determined at 5 hr after resuscitation. In a different setting, the effects of heme oxygenase blockade on the liver function was studied.;Our results show that phorbol-13-myristate-12-acetate (PMA)-stimulated O2- production was not influenced by T-H or gender. In contrast, N-formyl-methyonil-leucyl phenylalanine (fMLP)-stimulated O2-, and lipopolysaccharide (LPS)-stimulated elastase release by PMNs from male T-H rats was greater than that of females. A significant increase in MPO activity and in TBARS levels was observed in different tissue samples of animals of both sexes following T-H, however, MPO activity and TBARS levels were higher in males than in female rats. Levels of the chemokine citokine induced neutrophil chemoattractant (CINC-1) were elevated in the lungs of males, but not of proestrus females after T-H. Trauma-hemorrhage induced a two-fold increase in hepatic HO-1 expression in proestrus females compared to males. At the same time, hepatic expression of HO-2 was unaffected by gender or T-H. Blockade of HO with tin-protoporphyrin IX (SnPP) abolished the gender differences observed in HO-1 expression. This treatment also elevated the portal pressure, decreased bile production and increased ALT to similar levels in proestrus females and males following trauma-hemorrhage. As gender influenced the hepatic expression of HO-1 following trauma-hemorrhage, the enhanced induction of HO-1 expression and activity in females may act to attenuate hepatocellular dysfunction and injury probably by maintaining microcirculation. Moreover, the decreased PMN priming and activation in proestrus females, compared to males, occurs following trauma-hemorrhage resulting in decreased cellular injury and organ damage that is likely to contribute to improved outcome under those conditions.