| Background The etiology of acute liver failure is various,and the pathogenesis is complex.Nowadays,the role of intestinal mucosal barrier dysfunction caused by intestinal endotoxemia in the occurrence and development of liver failure has been paid more and more attention.The occurrence of intestinal endotoxemia is associated with ectopic intestinal bacteria,intestinal mucosal function barrier caused by intestinal mucosa damage,antibacterial ability declines,while intestinal alpha,beta defensins are antimicrobial peptides against intestinal pathogens in mammals,they can effectively resist the pathogens or displaced symbiotic bacteria,and maintain the intestinal mucosa biological barrier composed of normal flora.We don't have many reports about the changes of intestinal alpha,beta defensins in the occurrence of intestinal endotoxemia.Objective This study was conducted to investigate the dynamic changes of intestinal alpha-defensin-5,beta-defensin-2 m RNA after acute liver failure,and to explore their role in acute liver failure.Methods 90 C57BL6 mice were randomly divided into four groups: normal group,ALF group,E.coli via gavage group,ALF and E.coli via gavage group.Intraperitonealled D-Ga LN 500mg/kg and LPS 10?g/kg to made the model,in addition,ALF mice were fed with E.coli,the observation time was 6 hours,12 hours,and 24 hours,and each time point had 6 specimens,specimens from serum samples,tested ALT,AST levels;analyzed the pathological change of liver tissues and ileum tissues;used Real-Time PCR to test the RD-5 m RNA and BD-2 m RNA levels of the ileum tissue.Results(1)Compared with the normal group(11.25±0.74,23.86±0.39),in ALF group,the RD-5,BD-2 m RNA levels of ileum tissue increased at 6 hours,the valueswere 14.19±0.39(p<0.01),26.79±0.36(p<0.01),and peaked at 12 hours,the values were 15.76±0.33(p<0.01),29.10±0.61(p<0.01),and mildly increased at 24 hours,the values were 11.86±0.89(p<0.05),24.71±0.45(p<0.05);(2)Compared with the normal group(11.25±0.74,23.86±0.39),in ALF and E.coli via gavage group,the RD-5,BD-2m RNA levels of ileum tissue increased at 6 hours,the values were12.57±0.68(p<0.05),26.45±0.85(p<0.01),and peaked at 12 hours,the values were12.90±0.96(p<0.01),27.42±0.71(p<0.01);(3)Compared with the normal group(11.25±0.74,23.86±0.39),in E.coli via gavage group,the RD-5,BD-2 m RNA levels of ileum tissue peaked at 6 hours,the values were11.82±0.72(p<0.05),25.56±0.55(p<0.01),increased at 12 hours,the values were11.71±0.69(p<0.05),25.48±0.43(p<0.01),increased at 24 hours,the values were11.77±0.58(p<0.05),25.64±0.48(p<0.01);(4)Compared with ALF and E.coli via gavage group(the values were 12.57±0.68)and E.coli via gavage group(the values were 11.82±0.72),the RD-5 m RNA levels of ileum tissue in ALF group at 6 hours increased higher,the values were 14.19±0.39(p<0.01).Compared with ALF and E.coli via gavage group(the values were 26.45±0.85),the BD-2 m RNA levels of ileum tissue in ALF group,the difference was not statistically significant,the values were26.79±0.36(p>0.05),compared with E.coli via gavage group(the values were25.56±0.55),the values in ALF group increased higher(p<0.05).(5)Compared with ALF and E.coli via gavage group(the values were 12.90±0.96,27.42±0.71)and E.coli via gavage group(the values were 11.71±0.69,25.48±0.43),the RD-5,BD-2 m RNA levels of ileum tissue in ALF group at 12 hours increased higher,the values were15.76±0.33,29.10±0.61(p<0.01).Conclusion Alpha-defensin-5 and beta-defensin-2 may play an important role in the pathogenesis of intestinal endotoxemia in experimental acute liver failure. |
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