The Inhibition Effects Of Co-Releasing Molecules (CORM-2) On Inflammatory Response Of The Small Intestine In Early Sepsis And Molecular Mechanisms

The inhibition effects of CO-releasing molecules(CROM-2) on inflammatory response of the small intestine in early sepsis and molecular mechanismsBackground and objective:Sepsis refers to infections caused by SIRS and is confirmed the existence of bacteria or highly suspicious of infection.Sepsis is the difficult problem faced by trauma,burns surgical and ICU and its further development due to septic shock (septic shock,SS),acute respiratory distress syndrome(acute respiratory distress syndrome,ARDS),as well as integrated multi-organ dysfunction syndrome (multiple organ dysfunction syndrome,MODS),has become a leading cause of death in septic patients.Despite modern surgical techniques,care and antibiotic treatment has made great progress,the mortality rate of sepsis is still high, therefore,the prevention and treatment of sepsis and its complications in particular MODS is still one of the problems among contemporary science. Intestine is an important organ of body and its important physiological functions can not be ignored.In this study,the CO-releasing molecule(CORM-2) was used as an exogenous source of CO.Through in vitro and in vivo experiments we studied whether the exogenous CO could inhibit the inflammatory response of the small intestine of early sepsis and explored its mechanism.Method:The research is divided into 2 parts.In the first part,Caco-2 cell was stimulated by 15%CLP mouse serum to establish cells sepsis model as a sepsis model of the small intestine in vitro.The cells were used to study the mechanism of inflammatory response in vitro,as well as the intervention effect of the CO released by the CORM-2 on the role model.In the second part,use the C57BL/6 mice dealed with cecal ligation and puncture(CLP) as the in vivo model of sepsis.Mice were randomly divided into 4 groups(the number of specific cases may be based on the detection of targets):Sham-operated group,CLP group, CLP+iCORM group,CLP+CORM-2 group,the small intestine morphology, function,and inflammatory cells in CLP mice was used as an index to explore the molecular mechanisms.on early inflammatory responses in sepsis.The inhibition effect of exogenous carbon monoxide released by CORM-2 on the CLP mice's early intestinal inflammatory response was evaluated.Results and conclusions:1.Caco-2 Sepsis model:IL-8,NO levels improved,Inflammatory response in the CORM-2 group was significantly reduced than in the control group and thus to some extent,exogenous CO can inhibit the inflammatory response in Caco-2 model as in vitro model of intestinal sepsis.2.Sepsis model in CLP mice:24h after operation,the inflammatory cell infiltration of small intestine is obvious,the D/W lowered,peristaltic function lowered,plasma indicators such as IL-1β,IL-6,TNF-αsignificantly increased, ICAM-1,NF-κB and iNOS protein expression and NO,MDA,MPO levels significantly increased.The direct intervention of exogenous CO can significantly improve the degree of intestinal tissue swelling,enhance peristaltic function,inhibit inflammatory response and protect cells.These results show that the cell and animal models of sepsis demonstrated that the intervention of exogenous carbon monoxide somewhat inhibited the development of inflammatory response of early sepsis in the the small intestine.