肝脏 ›› 2016, Vol. 21 ›› Issue (1): 24-27.

• 论著 • 上一篇    下一篇

对乙酰氨基酚肝损伤时炎性因子、趋化因子以及Toll样受体表达的动态变化

金宇霆, 李大伟, 明雅南, 张江, 张明, 夏强   

  1. 200127 上海交通大学医学院附属仁济医院肝脏外科(金宇霆,李大伟,张江,张明,夏强); 消化内科(明雅南)
  • 收稿日期:2015-08-31 发布日期:2020-06-01
  • 通讯作者: 夏强,Email:xiaqiang@med mail.com.cn
  • 基金资助:
    国家自然基金项目(81472243); 上海市卫生局重点联合攻关项目(2013ZYJB001)

Dynamic variation of inflam matory cytokines,chemokines and Toll-like receptors in APAP-induced liver injury

JIN Yu-ting, LI Da-wei, MING Ya-nan, ZHANG Jiang, ZHANG Ming, XIA Qiang   

  1. Department of Liver Surgery,RenJi Hospital,ShanghaiJiao Tong University School of Medicine,Shanghai 200127,China
  • Received:2015-08-31 Published:2020-06-01
  • Contact: XIAQiang,Email:xiaqiang@medmail.com.cn

摘要: 目的 研究对乙酰氨基酚(APAP)引起肝脏组织损伤过程中的炎性因子、趋化因子以及Toll样受体的动态变化。方法 随机将30只小鼠分为6组:对照组、APAP1 h组、APAP3 h组、APAP6 h组、APAP12 h组,APAP24 h组,每组5只。禁食15 h后,对照组小鼠腹腔注射0.9%氯化钠溶液,其余5组腹腔注射APAP300 Mg/kg诱发小鼠肝损伤。取各组小鼠肝脏组织采用实时PCR检测炎性因子、趋化因子以及Toll样受体的MRNA水平,HE染色观察各组肝脏组织损伤情况。结果 与正常对照组相比,24 h内APAP诱发的小鼠肝损伤随时间推移加重。IL-6、IL-10、IL-1β、IP-10 MRNA相对于对照组在不同时间点有不同程度升高;MIP-3α 24 h相较对照组明显下降(P<0.05);IFN-γ和TNF-α各时间点变化差异无统计学意义。趋化因CXCR-2和CCR-2在24 h与对照组比较明显下降(P<0.05);CXCL-2分别在12 h 和24 h升高14.8倍(P<0.05)和7.8倍(P<0.05)。Toll样受体TLR-9、TLR-4相对对照组在不同时间点亦有不同程度升高或降低。结论 对乙酰氨基酚诱导肝损伤后,肝组织炎性因子、趋化因子及Toll样受体MRNA表达水平发生明显改变。

关键词: 对乙酰氨基酚, 炎症因子, 趋化因子, Toll样受体

Abstract: Objective To explore the dynamic changes ofinflam matory cytokines,chem okines and Toll-like receptors (TLR)in acetaminophen(APAP)-induced liver injury within 24 hours. Methods C57BL/6 mice were rando mly divided into six groups:control group,APAP1h group,APAP3h group,APAP6h group,APAP12h group and APAP24h group,including 5 mice in each group. After fasting for 15 hours,control group were given 0.9%saline by intraperitoneal injection,w hile other groups were given 300 Mg/kg APAP. Assessment of the various inflam matory cytokines,chem okines and TLRin mice liver was carried out at MRNAlevel by realtime poly merase chain reaction(RT-PCR). Degrees of APAP-induced liver injury were evaluated by haematoxylin eosin(HE)staining. Results According to HEstaining result,APAP-induced liver injury in APAPgroups increasingly aggravated within 24 hours w hen compared with that in control group.In APAPgroups,RT-PCRindicated that MRNAlevels of IL-6,IL-10,IL-1βand IP-10 rose to various degrees at different time points,w hile MIP-3α MRNAlevels declined distinctly(P<0.05),which was in contrast to control group. Additionally,variation ofinterferon(IFN)-γ and tu Mor necrosis factor(TNF)-α had no statistical difference between APAPand control groups.In APAPgroups,levels of CXCR-2 and CCR-2 were obviously lower at 24h(P<0.05)than those in control group,w hile level of CXCL-2 rose to 14.8 and 7.8 times higher at 12h and 24h(P<0.05),respectively. Furtherm ore,levels of TLR-9 and TLR-4 changed to various extents at different time points(P<0.05). Conclusion APAPfor 300 Mg/kg induces mice liver injury within 24h,which makes inflam matory cytokines,chem okines and TLRchange obviously at MRNAlevels in mice liver.

Key words: Acetaminophen, Cytokine, Chem okine, Toll-like receptor