Study on the injury effects and mechanisms of circulating histones on the hepatocytes of patients with hepatitis B virus-related liver failure
10.3760/cma.j.issn.1000-6680.2014.07.009
- VernacularTitle:乙型肝炎病毒相关肝功能衰竭患者循环组蛋白肝细胞损伤效应及其机制
- Author:
Xun JIANG
;
Lei GAO
- Publication Type:Journal Article
- Keywords:
Hepatitis B virus;
Liver failure;
Circulating histones;
Hepatocytes;
Anti-histone antibodies
- From:
Chinese Journal of Infectious Diseases
2014;(7):36-40
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the injury effects and mechanisms of circulating histones on the hepatocytes in patients with hepatitis B virus (HBV )-related liver failure (HBV-LF) .Methods Serum samples from patients with HBV-LF were collected . The levels of serum histone H3 , histone H4 , prothrombin activity (PTA ) ,total bilirubin (TBil) ,creatinine (Cr) and international normalized ratio (INR) of the patients were measured .Model for end-stage liver disease (MELD) score was calculated in the patients .The serum levels of histones were compared between patients and the healthy volunteers . The correlation of histones with the MELD score and PTA was analyzed .The human liver cell line L-02 cells were cultured and treated with the serum of patients or L-02 cellular lysate supernatant preincubated with or without anti-histone H3 and H4 antibodies .The cellular morphology and rate of apoptosis were observed .Intracellular calcium ion concentration and Caspase-3 activity were detected in the cultured L-02 cells treated with histones .Mean of two independent samples was compared using t tests .Relationship between histones and the MELD score or PTA was conducted using Spearman correlation analysis .Results The levels of serum histones in the patients with HBV-LF were much higher than those in the healthy volunteers (H3 :[5 390 .3 ± 1 032 .0] μg/mL vs [42 .7 ± 12 .8] μg/mL , t = 32 .76 , P < 0 .01 ; H4 :[4 205 .1 ± 662 .3] μg/mL vs [40 .3 ± 14 .6] μg/mL ,t = 39 .74 , P< 0 .01) .In addition ,serum histones (H3/H4) levels in patients were negatively correlated with serum PTA (r= - 0 .325 ,P= 0 .038 and r =- 0 .572 ,P= 0 .028 ,respectively) ,but positively correlated with the MELD score (r= 0 .359 ,P= 0 .021 and r = 0 .568 , P = 0 .007 , respectively ) . Both serum of patients with HBV-LF and L-02 lysate supernatant were toxic to cultured L-02 cells .The injury effect was inhibited by anti-histone antibodies ([9 .3 ± 1 .5]% vs [14 .3 ± 0 .6]% , t = 4 .259 , P= 0 .02) .L-02 cells treated with calf thymus histone were cultured for 4 h . Cellular toxicity of histones resulted in Caspase-3 activation . The effect was inhibited by anti-histone antibodies ([3 .5 ± 0 .5]% vs [5 .2 ± 0 .6]% ,t= 4 .243 ,P= 0 .02) .Conclusion The elevated circulating histones in the patients with HBV-LF may aggravate the liver damage .
