癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (3): 176-181.doi: 10.3969/j.issn.1004-616x.2018.03.003

• 论著 • 上一篇    下一篇

CD11c+细胞特异性敲除TAK1对刀豆蛋白A诱导的免疫性肝损伤的影响

周文娟, 雷志明, 魏雪涛, 郝卫东   

  1. 北京大学公共卫生学院毒理学系/食品安全毒理学研究与评价北京市重点实验室, 北京 100191
  • 收稿日期:2018-03-16 修回日期:2018-05-02 出版日期:2018-05-30 发布日期:2018-05-30
  • 通讯作者: 郝卫东,E-mail:whao@bjmu.edu.cn E-mail:whao@bjmu.edu.cn
  • 作者简介:周文娟,E-mail:zhouwenjuan225@163.com。
  • 基金资助:
    国家自然科学基金(81273112)

Effect of TAK1 knockout in CD11c+ cells on concanavalin A-induced liver injury

ZHOU Wenjuan, LEI Zhiming, WEI Xuetao, HAO Weidong   

  1. Department of Toxicology, School of Public Health, Peking University/Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China
  • Received:2018-03-16 Revised:2018-05-02 Online:2018-05-30 Published:2018-05-30

摘要: 目的:探讨CD11c+细胞中敲除TAK1对刀豆蛋白A(Con A)诱导的小鼠免疫性肝损伤的影响。方法:采用体内CD11c+细胞中特异性敲除TAK1的C57BL/6小鼠,经鼠尾静脉注射Con A(12 mg/kg)或生理盐水,分别作为Con A敲除组和生理盐水敲除组。另选C57BL/6小鼠,鼠尾静脉注射Con A(12 mg/kg)或生理盐水,作为Con A对照组和生理盐水对照组。给药6 h之后测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸转移酶(AST)和乳酸脱氢酶(LDH)水平;检测肝、肾、胸腺等脏器系数并进行肝组织病理学观察和评分;测定血清中免疫反应相关细胞因子肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白细胞介素(IL-4/5/6/12)及肝组织中TNF-α和IFN-γ的表达水平。结果:与生理盐水对照组相比,Con A对照组ALT和LDH显著升高(P均 < 0.05),肝脏病理损伤明显加重,病理评分显著升高(P < 0.05),血清中TNF-α、IFN-γ、IL-4/5/6水平和肝中TNF-α和IFN-γ均显著升高(P均 < 0.05);生理盐水敲除组肝中TNF-α水平显著降低(P < 0.05)。与Con A对照组相比,Con A敲除组小鼠血清ALT、AST和LDH水平均显著升高(P < 0.05),肝脏病理损伤明显加重,病理评分显著升高(P < 0.05),肝组织IFN-γ水平,血清中TNF-α、IL-4和IL-6水平均显著升高(P均 < 0.05)。结论:在本实验条件下,CD11c+细胞中敲除TAK1无明显肝损伤作用,但可加重Con A诱导的肝脏损伤,该作用可能与进一步激活免疫反应有关。

关键词: CD11c+细胞, 刀豆蛋白A, 免疫性肝损伤, 转化生长因子β激活激酶1

Abstract: OBJECTIVE: To explore the effect of TAK1 knockout in CD11c+ cells on concanavalin A (Con A)-induced immunological liver injury. METHODS: C57BL/6 mice with TAK1 knockout in CD11c+ cells were injected intravenously with normal saline or Con A (12 mg/kg) as NS+ and Con A (12 mg/kg)+ knockout groups,respectively. Normal C57BL/6 mice were injected intravenously with normal saline or Con A (12 mg/kg) as NS+ and Con A (12 mg/kg)+ control groups,respectively. After 6 hours,serum was collected to detect the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactic dehydrogenase (LDH). Organ coefficients of liver,kidney,thymus and other organs were detected. Histopathological observations and scores were performed. Serum was collected to detect the expression of tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ) and interleukins (IL-4/5/6 and IL-12). The levels of TNF-α and IFN-γ in liver were detected. RESULTS: Compared with NS+ control group,levels of ALT and LDH were significantly increased in Con A+ control group (P < 0.05). Con A+ control group showed severer pathological liver injury and higher pathological score (P < 0.05). The levels of TNF-α,IFN-γ,IL-4,IL-5,IL-6 in serum and TNF-α and IFN-γ in liver were significantly increased (P < 0.05). Compared with NS+ control group,the level of TNF-α in liver in NS+ knockout group was significantly decreased (P < 0.05). Compared with Con A+ control group,levels of ALT,AST and LDH were significantly increased in Con A+ knockout group (P < 0.05). Con A+ knockout group showed severer pathological liver injury and higher pathological score. The levels of TNF-α,IL-4 and IL-6 in serum and IFN-γ in liver were significantly increased (P < 0.05). CONCLUSION: Knockout of TAK1 in CD11c+ cells was not related to liver injury but aggravated concanavalin A-induced immunological liver injury.

Key words: CD11c+cell, concanavalin A, immunological liver injury, TGF β-activated kinase 1

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