Changes of extracellular histones in mice with acute liver failure and its therapeutic potential
10.3760/cma.j.issn.1671-0282.2013.02.009
- VernacularTitle:细胞外组蛋白在急性肝衰竭小鼠中的变化
- Author:
Tao WEN
;
Chunyan GOU
;
Jing LU
;
Yan LIU
;
Zhengfu PIAO
;
Feng LI
;
Dexi CHEN
- Publication Type:Journal Article
- Keywords:
Extracellular histones;
Acute liver failure;
Cell apoptosis;
Neutralizing antibody;
Inflammation;
TNF-α
- From:
Chinese Journal of Emergency Medicine
2013;22(2):148-152
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the changes of extracellular histones during the course of acute liver failure in mice as well as its therapeutic potential.Methods WT mice (C57BL/6) were randomly (random number) allocated to inducing acute liver failure by lethal doses of GalN/LPS injected i.p.Hepatic function,apoptosis of hepatocytes and histological indexes were measured at different intervals following GalN/LPS challenge.The levels of extracellular histones were determined by using ELISA and Western blot methods.Meanwhile,GalN/LPS-treated mice were administered with anti-histone H3 and antihistone H4 neutralized antibodies,respectively.Results Administration of GalN/LPS to mice caused acute liver failure,characterized by significant elevation of plasma ALT levels and massive hepatocyte apoptosis or necrosis.All mice died within 9-12 hours.The levels of nucleosomes and extracellular histones H3 and H4 were increased considerably in a time-dependent manner.The survival rates in GalN/LPS-treated mice were improved remarkably following administration of anti-histone H3 and H4 neutralized antibodies (P =0.037,P =0.025),likely due to the significant inhibition of TNF-production.Conclusions Extracellular histones are an important mediator implicated in the pathogenesis of acute liver failure.Anti-histones show promising potential in the treatment of acute liver failure,which deserves further investigation in the future.
