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The Inhibition Effects of Co-Releasing Molecules (CORM-2) on Inflammatory Response and Phospholilation of JAK of the Liver in Sepsis and Molecular Mechanisms

Author: ShiGengSheng
Tutor: SunBingWei
School: Jiangsu University
Course: Surgery
Keywords: CORM-2 inflammation the Liver sepsis inhibition effects
CLC: R459.7
Type: Master's thesis
Year: 2010
Downloads: 46
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Abstract

Background 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.As an important organ,the Liver plays a vital role in the occurrence and development of sepsis and its important physiological functions can not be ignored,the acute-phase proteins and cytokines released by liver cell and kuffer cell play an important role in sepsis.The liver has the largest number of full-body macrophages,responsible for eliminating from the intestinal LPS and bacteria,so it plays an important role in the SIRSIn 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 Liver of early sepsis and explored its mechanism.Method:The research is divided into 2 parts.In the first part,Monocyte-derived macrophages was stimulated LPS to establish cells sepsis model as a sepsis model of the Liver 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 Liver 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 liver inflammatory response was evaluated.Results and conclusions:1.Monocyte-derived macrophages Sepsis model:The phosphorylation levels of and the IL-1β,TNF-αlevel in the culture media in LPS-stimulated Monocyte-derived macrophages increased significantly.ICAM-1,JAK1/JAK3 protein expression was significantly increased.Inflammatory response in the exogenous CO intervention group was significantly reduced than in the control group and thus to some extent,exogenous CO can inhibit the inflammatory response in RAW264.7 model as in vitro model of the Liver sepsis.2.Sepsis model in CLP mice:24h after operation,the inflammatory cell infiltration of liver is obvious,plasma indicators increased significantly,ICAM-1, JAK1/JAK3 protein expression significantly increased.The direct intervention of exogenous CO can significantly improve the degree of liver 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.

The Inhibition Effects of Co-Releasing Molecules (CORM-2) on Inflammatory Response and Phospholilation of JAK of the Liver in Sepsis and Molecular Mechanisms

Abstract

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