Effect Of Ulinastatin On Survival And Immune Function In Mice With CLP-induced Sepsis

ObjectiveThe aim of this study is to through observing the changes of survival, cytokines and lymphocytes to investigate the probalble mechanism of ulinastatin in mice with CLP-induced sepsis.Methods8～10 weeks male C57BL/6 mice were randomly assigned into four groups, i.e., Sham, CLP (cecal ligation and puncture), CLP plus UTI (100 000 U/kg) by intraperitoneal injection (UTI ip) at half an hour after operation and CLP plus UTI (100 000 U/kg) by intravenous injection (UTI iv) at half an hour after operation. After successfully founding the CLP model, a 7 days survival observation with each group 10 mice was made and the survival rate curve also was described. On the basis of 7 days survival, all groups were studied once again with each group 10 mice after 24h of CLP. Detect index including: Pro-inflammatory cytokines (TNF-αand IL-6) and anti-inflammatory (IL-10) will be checked; Lymphocytes count in Peripheral blood, thymus and spleen; The apoptosis of lymphocytes in thymus and spleen; The weight of thymus and spleen; H&E staining after formaldehyde fixing will be checked under microscope. All statistics were done with Prism5.01 (GraphPad Software, USA). Results7 days survival in UTI groups were higher than that in CLP group (p<0.05); TNF-αand IL-6 level in UTI groups decreased more significant than that in CLP group(p<0.05), IL-10 level in UTI groups increased more significant than that in CLP group(p<0.05); Lymphocyte count in UTI groups increased more significant than that in CLP group(p <0.05);The thymus weight in UTI groups increased more significantly than that in CLP group(p<0.05).Under microscope, the structure of lobule of thymus maintained in UTI groups but diffused in CLP group. Both cortex lymphocyte and medullary lymphocyte decreased apparently in CLP group. There were no significant difference in spleen weight(p>0.05).The structure of red medullary and white medullary maintained in UTI groups and splenic nodule could be seen. The structure of red medullary and white medullary diffused in CLP group and splenic nodule could not be seen. All results between UTI ip and UTI iv had no statistically significant (p>0.05). ConclusionsUTI treatment in sepsis mice could decrease TNF-αand IL-6 and increase IL-10; UTI treatment in sepsis mice could increase lymphocytes count; UTI treatment in sepsis mice could alleviate the lymphocytes apoptosis of thymus and spleen. The UTI treatment could improve the survival of sepsis mice.