粒细胞集落刺激因子对小鼠内毒素性急性肝损伤的保护作用

Protective effects of granulocyte colony stimulating factor on acute liver injury induced by lipopolysaccharide in mice

目的观察粒细胞集落刺激因子对小鼠内毒素性急性肝损伤的作用,并对其机制进行初步探讨。方法昆明(KM)小鼠随机分为模型组、预防组和正常组,模型组小鼠腹腔注射内毒素(LPS)10mg/kg或30mg/kg,预防组于造模前1小时皮下注射重组人粒细胞集落刺激因子(rhG-CSF)500μg/kg,正常组注射等剂量的生理盐水,观察各组小鼠的存活率及造模后6h、24h小鼠肝脏组织病理变化,全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的水平,酶联免疫吸附试验(ELISA)检测血清肿瘤坏死因子(TNF-a)和白介素-10(IL-10)的水平。结果预防组小鼠存活率与模型组相比无明显差异(80%vs 66.7%,P>0.05);预防组肝组织损伤及肝功能酶学指标ALT和AST均好于模型组(P<0.05);预防组小鼠血清IL-10的表达水平在6小时点明显高于模型组(P<0.05),24小时点与模型组相比无明显差异(P>0.05),血清TNF-a表达水平与模型组相比差异无统计学意义(P>0.05)。结论粒细胞集落刺激因子对小鼠内毒素性急性肝损伤具有保护作用,对小鼠的存活率无明显影响。

Objective To investigate the effect of recombinant human granulocyte colony stimulating factor （ rhG-CSF ） on acute liver injury induced by lipopolysaccharide （ LPS ） in mice,and to make prelim- inary discussion on its mechanism. Methods The KM mice were divided randomly into 3 groups, model, prevention and normal. The mice were intraperitoneally infected with LPS（10 mg/kg or 30 mg/kg）（the model group） ,or with either rhG-CSF at 500 g/kg body weight（the prevention group）or saline（the nor- mal group）at lh before LPS injection. The survival rate of the mice was estimated after LPS injection. The degree of hepatic injury was evaluated at 6 h and 24h after LPS injection, and the level of alanine ami- notransferase （ALT） and aspartate aminotransferase（AST） in the serum was measured by an automatic biochemical analyser. Serum TNF-a and IL-10 levels were determined by ELISA. Results There was no significant difference between prevention and model groups in the survival rate（80G vs 66.7 G ,P;〉0.05）. Compared with the model group,the change of liver histology and the levels of ALT and AST were signifi＋ cantly lower in the prevention group（P〈0.05） the level of serum IL-10 was significantly increased than in the model group at the 6h point（P〈0.05） ,while there was no significant difference at the 24h point（P 〉0.05）. The prevention group showed similar serum levels of TNF-a at any time point to the model group（P〉0.05）. Conclusion RhG-CSF can protect mice from acute liver injury induced by LPS, but it can not enhance the survival rate of mice with endotoxemia.