Establishment Of A Sepsis Model By CLP And Influence Of Antimicrobial Peptide Lycosin-1on The Kidney And Liver Of Mices With Sepsis

Objectivesepsis develops from the systemic inflammatory response syndrome,whice can caused by bacteria、fungi、viruses,while severe sepsis will develop into multiple organ failure and septic shock.Excessive activation of the inflammatory response and immune disorders play important roles in sepsis.Cecal ligation and puncture (CLP) may cause abdominal mixed bacterial infection,induce acute peritonitis,and then sepsis.This method is widely used in study of mechanism and treatment of sepsis.Antimicrobial peptides are small amphiphilic peptides, With broad-spectrum antimicrobial activity、anti-inflammatory and immune regulation,widely present in prokaryotic and eukaryotic organisms. Lycosin-1(Lye) belongs to cationic antimicrobial peptides. However it is not well known that whether antimicrobial peptides have adverse effects on mammal’s liver and kidney.This research was designed to investigate the effects of Lye on normal and septic Balb/c mice’s liver and kidney function.Methods Firstly,a mice model of sepsis was established by CLP. Secondly, Five different concentration subgroups of Lyc,25ug/ml、50ug/ml、100ug/ml、200ug/ml、500ug/ml,was injected intraperitoneally in order to observe toxicity to livers and kidneys.Last part was to investigate the protective effect of200ug/ml Lyc on the acute livers and kidneys injures in sepsis.The mices were randomly divided into4groups:(1) sham-operated control group;(2)sham-operated group with200ug/ml Lyc;(3)CLP group;(4)CLP group with200ug/ml Lyc.Lyc was injected intraperitoneally after CLP operation,and the control groups was injected intraperitoneally with equal volume saline.serum contents of creatinine(Cr)、Urea nitrogen(BUN)、Alanine aminotransferase(ALT)、 Aspartate aminotransferase(AST) were tested.Results(1) The stable CLP mice model was established.(2)No mice died during the observation period,Compared with the control group,Five different concentration subgroups of Lyc,the liver and kidney indicators did not change signiflcantly(P>0.05).(3)Compared with the sham group,serum concentration values of Cr、BUN、ALT、AST in CLP group were increased at6h after surgery(P<0.05).While When Compared with the CLP group,the values of Cr、BUN、ALT、AST in Lyc intervention group did not reduce, but more significantly increased(P<0.05). Conclusion(1)We successfully conducted a moderate/severe model of sepsis with Cecal ligation and puncture.(2)Lyc, without acute toxicity to normal mice’s liver and kidney function,However, no protective effect, and may even exist side effects for sepsis-induced livers and kidneys injury in mice.