The Study On Relationship Between Int Erllukin-8 And Liver Injury Of Rats Causing By Endotoxicemia And Interverntion Of Recombinant Granulocyte-Colony Stimulating Factor

Objective: we established endotoxemia rat models to study the changes of liver cells during endotoxemia by determining the levels of ALT and AST in serum and observing liver pathological change of these rat's by light microscope. Then detect the level of IL-8/CINC to investigate the function of rG-CSF in reducing the levers of IL-8 in liver and serumMethod: 72 rats of 18-day-postnatal were randomly divided into NS control group(NS, n=18),lipopolysaccharide group(LPS, n=18) and rG-CSF treated group (rG-CSF+LPS, n=18) ,CSF control group (rG-CSF+NS, n=18). According to the survival time , each group has been divided into 3h﹑6h and 12h 3 subgroups,each subgroup has 6 rats. The baby rats in Sodium Chloride of the same dose were injected group were injected lipopolysaccharide into abdominal cavity at a dose of 5mg/kg , lipopolysaccharide had been attenuated to 0.8mg/ml by Sodium Chloride. In the normal control group , Sodium Chloride of the same dose were injected . Rats in the rG-CSF+LPS group were given rG-CSF(250μg/kg) subcutaneous 30 min before lipopolysaccharide injected. In the rG-CSF control group, 250μg/kg of CSF was injected subcutaneously 30 min before NS instillation. After the rats were killed , We collected the liver and blood samples and tested the level ALT and AST in serum , IL-8 lever were also detected by ELISA and immunohistochemistry. At the same time, we observed the liver changes of these rats by light microscope.Results: No liver injury was found in the normal control group and rG-CSF control group .But the rats'livers in LPS group were damaged seriously ,in which the exudation, edema, hyperemia ,degeneration ,necrosis and apoptosis could be found. 6 hour is the worst piont. Compare to LPS group at the same time piont, rG-CSF +LPS group had slighter injury in liver cells. In the lipopolysaccharide groups,the levels of IL-8/CINC in liver and serum,AST and AST in serum were much higher than NS group,especially at 6 hour point. The IL-8/CINC,ALT and AST in rG-CSF treated groups were lower than LPS group at 12h,but still higher compared with that of in NS group and rG-CSF control group.Conclusions1. Endotoxemia could induce liver injury. After lipopolysaccharide was injected into abdominal cavity , the levels of ALT and AST in serum were raised. Meanwhile, the cellular edemade ,fatty degeneration,apoptosis ,necrosis and Inflammatory cell infiltration were found. Indicating that liver is one of the main organs which involved in severe infection.2. We found IL-8/CINC was raised when endotoxemia happened , it's lever was related with the liver injury . IL-8/CINC may participated in the liver damage.3. We also found that pretreatment with rG-GSF attenuated lipopolysaccharide induced liver injury,the mechanism may be that the rG-GSF could decrease the production of IL-8/CINC.