| Backgroundand objectiveSepsis is a clinical syndrome that complicates severe infection. Sepsis, which morbidity and mortality remains high, is an important cause of death in clinical. Recently in the United States, the incidence of severe sepsis has been estimated to be 3% of the population, with a death rate of 25% among these cases during hospitalization. Clinically, nearly 95% of sepsis cases are caused by bacterial infection, and 62.2% of these can be attributed to Gram-negative bacteria, with Escherichia coli(E coli.) responsible for nearly 16% of these infections. E coli.is an opportunistic pathogen, which migrates by bacterial translocation from the gastrointestinal tract to extra-intestinal sites, where virulence factors are important in establishing infections. The aim of the present study was to determine the capacity oexogenous CO, carbon monoxide-releasing molecule II(CORM-2), to significantly suppress E coli. ATCC25922 vitality, and to decrease the inflammatory responses in the liver and lung,increase the survival rate in an E coli.-induced murine model of sepsis.MethodsThis study consists of two main parts. In the first part, measurement of growth curve was used to dynamically study the growth of bacteria, and we focused on how CORM-2 altered the duration of the lag phase.In the second part, ICR male mice were randomly divided into 4groups control group,E coli. group(treated with the E coli. i.p 5m L), E coli.+CORM-2 and E coli.+i CORM-2(treated as sepsis group following administration of i CORM-2 and CORM-2i.v 8mg/kg, respectively). Survival rates were measured. Serum, liver and lung tissues were collected at 6 h after bacterial infection. Serum LPS was assayed using Limulus amebocyte lysate tests. TNF-α and IL-1β in serbiochemical methods. Neutrophil infiltration of tissues was evaluated by myeloperoxum and tissues were assayed by ELISA. Serum aminotransferases were assayed by idase activity detection. Bacteria in peritoneal lavage fluid,blood and liver and lung tissues were enumerated following culture. Tissue i NOS m RNA expression was detected by RT-PCR. NF-κB expression was detected by western blot.Results1.Bacterial growth was markedly suppressed in the presence of CORM-2. This was confirmed by observing growth curve of E coli. under intervention of CORM-2 or i CORM-2. When compared with E coli. and E coli. + i CORM-2 group, the growth of E coli. in E coli. +CORM-2 group was suppressed, and the point the entering platform phase was significantly delayed, with a decrease in colony numbers.2.CORM-2 treatment significantly increased the survival rate in sepsis mice. Compared with control group, obvious pathological changes were observed in the E coli. group.Myeloperoxidase activity, expression of TNF-α, IL-1β and serum transaminases were also significantly enhanced. In contrast, compared with E coli. and E coli.+i CORM-2 group,CORM-2 treatment resulted in decreases in tissue MPO activity, expression of inflammatory factors and transaminases. The number of colonies in blood, peritoneal lavage fluid(PLF),liver and lung were significantly decreased in E coli.+i CORM-2 group compared with E col and E coli.+i CORM-2 groups. Meanwhile, the number of colonies and the expression of i NOS m RNA and NF-κB in the major organs of E coli. +CORM-2 group was significantly decreased compared with that in the E coli. and E coli.+i CORM-2 group.ConclusionsIn addition directly suppressing E coli., CORM-2 protects the liver and lungs against E coli.-induced sepsis in mice by interfering with NF-κB activation, and thus improving their survival. |
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