The effects of activated protein C on epithelial apoptosis in intraabdominal rat sepsis model

Objective:In recent years, there are evidences that apoptosis is the major determinant on the results of sepsis syndrome and is the most important cell death mechanism in sepsis and endotoxemic processes. Antiapoptotic treatment trials are started to become important in increasing the lifetime expectance. In this study, it is aimed to investigate the effects of activated protein C (APC) on epithelial apoptosis in rat sepsis model.Method:After the approval of ethics committee for Research Animals, 21 adult male Wistar Albino rats were randomly allocated into three groups: group Sham (n=7), group Sepsis (n=7), group Sepsis+APC (n=7); in sham group only laparotomy was performed. CASP surgery was performed in the sepsis group and intravenous serum physiologic infusion was administered. In Sepsis+APC group after CASP surgery, infusion of APC was administered. At the end of the study a median sternotomy was performed under general anesthesia and rats were sacrified by aspirating blood from left ventricles of the rats; lung and jejenum samples were collected. Serum soluble CK18 (cytokeratine 18) neoepitop M30 level was determined biochemically using ELISA method. Alveolar macrophage quantity and intestinal mucosal injury was assessed histopathologically (Chiu score). In comparison of three groups for nominal values one-way variance analysis (ANOVA) was performed and in couple group comparisons Mann-Whitney U test was used and p< 0.05 were regarded as statistically significant.Results:Serum M30 level in Sepsis group was significantly higher than in sham group (p:0.02). On the other hand, serum M30 levels in Sepsis+APC group were not significantly higher than sham group (p:0.23). There was no significant reduction in M30 level in Sepsis+APC group than in Sepsis group(p:0,09).Jejenum Chiu scoring was significantly higher in Sepsis group than in sham group (p:0,001). Chiu scoring was significantly lower in Sepsis+APC group than in Sepsis group. (p:0,002). Jejenum Chiu scoring was significantly higher in Sepsis+APC group than in sham group.(p: 0,002).Alveolar macrophage quantity was significantly higher in Sepsis group than in sham group (p:0,002). The alveolar macrophage quantity in Sepsis + APC group was significantly lower than in Sepsis group (p:0,001).Furthermore, alveolar macrophage quantity in Sepsis +APC group was significantly higher than in sham group (p:0,001).Conclusion:In conclusion, serum M30 levels in APC administered group were not increased as the ones in sepsis group and in APC administered group Chiu scoring and alveolar macrophage quantity were significantly lower than the ones in sepsis group. As a result of this, the effects of APC on epithelial apoptosis in sepsis should be investigated in further studies.