A Study Of Prostaglandin E₂on Alleviating Liver Indury And Enhancing Liver Regeneration Acute Liver Failure In Mice

Part ⅠThe Role of Prostaglandin E2in Alleviating Liver Indury in Acute Liver Failure in MiceAims:To investigate the role of prostaglandin E2(PGE2) in alleviating acute liver injury induced by acetaminophen (APAP) in mice.Methods:Eight-week ICR mice were randomly divided into three groups:(1) the normal control group:normal mice treated with saline;(2) the liver failure group: APAP-induced liver failure mice treated by phosphate buffer saline; and (3) PGE2-treated group:APAP-induced liver failure mice treated by dmPGE2; The mice were killed and samples were obtained at12hours,24hours,48hours after APAP administration, respectively. Serum alanine aminotransferase (ALT) and total bilirubin (TBIL) were measured and sections of liver were prepared for histological examination.Results:The level of serum ALT of the liver failure group mice was elevated at12h,24h,48h after APAP administration comparing to normal mice; and it was lower in PGE2treated mice at12h and24h comparing to the live failure group (P<0.05), while there was no significant difference at48h (P>0.05). The level of serum TBIL of liver failure mice was elevated at12h after APAP administration comparing to normal mice whereas down-regulated in mice of PGE2-treated group(P<0.05); however, no significant difference were found among the three groups at24h and48h (P>0.05). Severe liver damage was observed at12h after APAP administration by histological examination, and the degree of liver injury of the mice in liver failure group at12h,24h,48h were4.0±0.7,3.8±0.8,2.4±1.1, respectively; while he degree of liver injury of the mice in PGE2-treated group at12h,24h,48h were1.4±0.5,2.2±0.8,1.2±0.4, respectively. The PGE2group showed slighter liver injury than the liver failure group (P<0.05).Conclusions:PGE2can alleviate APAP-induced acute liver injury in mice and facilitate the recovery of the liver. It might be a potential medication for treating liver failure. Part ⅡThe Effect of Prostaglandin E2in Liver Regeneration of Acute Liver Failure in Mice and the Correlationship with HGF, Wnt2and β-cateninAims:To investigate the effect of PGE2in enhancing liver regeneration in mice with APAP-induced acute liver failure and the role of HGF, Wnt2and β-catenin in regulation of liver regeneration by PGE2.Methods:Proliferating cell nuclear antigen (PCNA) which indicating the level of liver regeneration was evaluate by immunohistochemistry on sections of paraffin-embedded liver tissue. The expression of HGF, Wnt2and β-catenin was evaluated by reverse transcription-polymerase chain reaction and western blot.Results:The rate of PCNA-positive cells in liver of liver failure mice group was down-regulated at12h and24h after APAP administration comparing to normal group, but the difference did not reach the statistic significance (P>0.05); and it was up-regulated at48h (15.4±4.8%vs10.0±1.9%, P<0.05). Treatment of PGE2up-regulated the rate of PCNA-positive cells at24h and48after APAP administration respectively, comparing to other groups (P<0.05). The expression of HGF and (3-catenin mRNA was up-regulated in mice of PGE2-treated group comparing to liver failure group(P<0.05), while there was no significant difference between normal group and liver failure group(P>0.05). The expression of Wnt2mRNA was up-regulated in PGE2-treated group comparing to liver failure group at12h after APAP-administration(P<0.05). The level of β-catenin and Wnt2protein showed no changed by western blot; while the level of HGF protein was up-regulated in mice of PGE2-treated group comparing to liver failure group at12h and24h, respectively.Conclusions:PGE2was capable of enhancing liver regeneration in mice with APAP-induced acute liver failure and this effect might correlate to HGF and β-catenin.