【摘要】 目的 :研究不同剂量的新型重组人肿瘤坏死因子 (nrhTNFα)对肝功能及肝脏组织形态学的影响。方法 :用四氯化碳 (CCl4)或刀豆蛋白A(ConA)诱导小鼠肝损伤 ,nrhTNFα低、中、高剂量 (5× 10 4,5×10 5,5× 10 6IU·kg-1)im ,测血清中ALT、AST、LDH、IFN α、IL 2和NO浓度变化 ,检查肝脏组织形态学变化。结果 :3个剂量的nrhTNFαim对正常小鼠肝功能及肝脏组织形态学无影响 ;低、中剂量nrhTNFα对CCl4诱导肝损伤小鼠的肝功能及肝脏组织形态学无影响 ,高剂量nrhTNFα加重肝损伤 ;3个剂量的nrhTNFα降低ConA诱导的肝损伤小鼠血清ALT、AST、LDH和IFN γ浓度增加 ,且nrhTNFα低剂量作用明显 ,能明显减轻肝脏病理学改变。结论 :nrhTNFα低、中、高剂量im对正常小鼠无肝毒性 ;nrhTNFα低、中剂量im不影响CCl4诱导的肝损伤 ,高剂量则加重之 ;3个剂量的nrhTNFαim抑制ConA诱导的肝损伤 ,其作用机理与抑制ConA诱导的小鼠IFN γ产生有关。更多还原

【Abstract】 AIM: To investigate the effects of different doses of nrhTNFα on liver function and liver histological morphology and explore its mechanism. METHODS: Liver injury was induced by CCl 4 or Concanavalin A (Con A) in mice. nrhTNFα(IU·kg -1 )was injected intramuscularly at low(5×10 4), median(5×10 5), and high doses(5×10 6).Changes of serum ALT, AST, LDH, IFN γ, IL 2 and NO levels were detected. Liver histological changes were examined accordingly. RESULTS: The nrhTNFα had no effect on the liver function and liver histological morphology in intact mice at above three doses groups. The nrhTNFα also had no effect on the liver function and liver histological morphology in the CCl 4 treated mice at the low and median doses groups, but liver damage was exacerbated at the high dose group in this model. The increased concentrations of serum ALT, AST, LDH and IFN γ levels in the Con A treated mice were diminished with three doses groups, especially at the low dose group. A significant improvement was observed in pathohistology examination in this model at above three doses groups. CONCLUSION: The nrhTNFα im has no hepatic toxicity in intact mice at above three doses groups. The low and median doses of nrhTNFα im have no impact on the liver injury in the CCl 4 treated mice. The high dose of nrhTNFα im exacerbates the liver injury in this model. The nrhTNFα inhibits the liver injury in the Con A treated mice. Its mechanisms may be related to the inhibition of the production of IFN γ in this model.更多还原