新型重组人肿瘤坏死因子-α对四氯化碳及刀豆蛋白A 诱导小鼠肝损伤的影响

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (2): 196-200.

新型重组人肿瘤坏死因子-α对四氯化碳及刀豆蛋白A 诱导小鼠肝损伤的影响

石传群, 吴勇杰, 高明堂, 李文广, 臧凯宏, 李智勤

兰州大学药学院, 甘肃省中药新药临床前研究重点实验室, 兰州730000, 甘肃

收稿日期:2004-11-01 修回日期:2004-12-06 出版日期:2005-02-06 发布日期:2020-11-18
通讯作者: 吴勇杰, 男, 教授, 硕士生导师, 研究方向:生物技术药品的临床前研究。Tel:0931-8623573 E-mail:lywyj@r5you.com
作者简介:石传群, 女, 硕士, 药师。Tel:0931-3853143 E-mail:scq3853143@tom.com

Effects of novel recombinant human tumor necrosis factor α(nrhTNFα) on liver injury induced by carbon tetrachloride or Concanavalin A

SHI Chuan-qun, WU Yong-jie, GAO Ming-tang, LI Wen-guang, ZANG Kai-hong, LI Zhi-qin

College of Pharmaceutical Science of Lanzhou University, Key Laboratory of Preclinical Study for New Traditional Chinese Medicine of Gansu Province Lanzhou, 730000, Gansu, China

Received:2004-11-01 Revised:2004-12-06 Online:2005-02-06 Published:2020-11-18

摘要/Abstract

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(Con A)诱导小鼠肝损伤, nrhTNFα低、中、高剂量(5×10⁴, 5×10⁵, 5×10⁶ IU°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Con A 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Con A诱导的肝损伤, 其作用机理与抑制Con A 诱导的小鼠IFN-γ产生有关。

关键词: 肿瘤坏死因子-α, 肝损伤, 刀豆蛋白A, 四氯化碳, 干扰素-γ, 小鼠

Abstract: AIM: To investigate the effects of different doses of nrhTNFαon liver function and liver histological morphology and explore its mechanism.METHODS: Liver injury was induced by CCl4 or Concanavalin A (Con A)in mice.nrhTNFα(IU°kg^-1)was injected intramuscularly at low(5×10⁴), median(5×10⁵), and high doses (5×10⁶).Changes of serum ALT, AST, LDH, IFN-γ, IL-2 and NO levels were detected.Liver histological changes were examined accordingly.RESULTS: The nrhTNFαhad no effect on the liver function and liver histological morphology in intact mice at above three doses groups.The nrhTNFαalso had no effect on the liver function and liver histological morphology in the CCl4-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-γlevels 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 nrhTNFαim has no hepatic toxicity in intact mice at above three doses groups.The low and median doses of nrhTNFαim have no impact on the liver injury in the CCl4-treatedmice.The high dose of nrhTNFαim exacerbates the liver injury in this model. The nrhTNFαinhibits the liver injury in the Con A-treated mice.Its mechanisms may be related to the inhibition of the production of IFN-γin this model.

Key words: tumorne crosis factor-α, liver injury, Concanavalin A(ConA), carbon tetrachloride, interferon-γ, mice

中图分类号:

R979.1

石传群, 吴勇杰, 高明堂, 李文广, 臧凯宏, 李智勤. 新型重组人肿瘤坏死因子-α对四氯化碳及刀豆蛋白A 诱导小鼠肝损伤的影响[J]. 中国临床药理学与治疗学, 2005, 10(2): 196-200.

SHI Chuan-qun, WU Yong-jie, GAO Ming-tang, LI Wen-guang, ZANG Kai-hong, LI Zhi-qin. Effects of novel recombinant human tumor necrosis factor α(nrhTNFα) on liver injury induced by carbon tetrachloride or Concanavalin A[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(2): 196-200.

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