8-oxo-Guo调控小鼠细胞因子表达及肺泡巨噬细胞极化的研究  

Research on the regulation of cytokine expression and alveolar macrophage polarization by 8-oxo-Guo in mice

作　　者：李瑞 李瑾[1] 蔡剑平[1] LI Rui;LI Jin;CAI Jianping(The Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing Hospital/National Center of Gerontology of National Health Commission,P.R.China,Bejing 100730,China.)

机构地区：[1]北京医院,国家老年医学中心,国家卫生健康委北京老年医学研究所,国家卫生健康委老年医学重点实验室,中国医学科学院老年医学研究院,100730

出　　处：《中国老年保健医学》2025年第1期3-8,共6页Chinese Journal of Geriatric Care

基　　金：中央高校基本科研业务费专项资金资助(编号:BJ-2023-276);中央高水平医院临床科研业务费(编号:BJ-2023-246)。

摘　　要：目的明确核酸氧化损伤代谢产物8-oxo-Guo对小鼠体内细胞因子产生及肺泡巨噬细胞极化的影响,探讨其在肺部免疫炎症中的潜在作用。方法选用10~12周龄C57BL/6N雄鼠,随机分为对照组和8-oxo-Guo组,每组6只。8-oxo-Guo组小鼠尾静脉注射8-oxo-Guo(溶于含10%小鼠血清的1×PBS中,剂量为4μg/kg),对照组注射等体积含10%小鼠血清的1×PBS。间隔2小时注射1次,共注射2次,4小时后收集小鼠肺泡灌洗液和血浆。然后采用RayBio■QAM-CAA-4000芯片检测200种血浆细胞因子浓度,通过流式细胞术检测肺泡巨噬细胞极化情况。使用SPSS 22.0软件进行数据分析,以未配对Student t检验分析两组间差异,P<0.05为有统计学意义。结果与对照组相比,8-oxo-Guo组小鼠血浆中IL-12 p70、MIP-2等多种细胞因子显著上调,IL-33显著下调;GO富集分析显示变化的细胞因子主要在免疫效应调节等功能方面富集且与细胞对脂多糖反应相似。肺泡巨噬细胞检测中,8-oxo-Guo组小鼠肺泡巨噬细胞CD86^(+)CD206^(-)细胞占比率及CD86^(+)荧光强度增加,表明8-oxo-Guo可以诱导肺泡巨噬细胞向M1型极化。结论本研究基于小鼠模型证明8-oxo-Guo引起小鼠血浆细胞因子产生上调和肺泡巨噬细胞的促炎型转换,提示8-oxo-Guo可能在肺部免疫炎症进程中起重要作用。Objective To clarify the effects of 8-oxo-Guo,a metabolite of nucleic acid oxidative damage,on the production of cytokines in mice and the polarization of alveolar macrophages,and to explore its potential role in pulmonary immune-inflammation.Methods C57BL/6N male mice aged 10~12 weeks were randomly divided into a control group and an 8-oxo-Guo group,with 6 mice in each group.Mice in the 8-oxo-Guo group were injected via the tail vein with 8-oxo-Guo(dissolved in 1×PBS containing 10%mouse serum at a dose of 4μg/kg),while the control group was injected with an equal volume of 1×PBS containing 10%mouse serum.The injection was repeated every 2 hours for a total of 2 times.Four hours after the last injection,bronchoalveolar lavage fluid and plasma of the mice were collected.Subsequently,the RayBio■QAM-CAA-4000 chip was used to detect the concentrations of 200 plasma cytokines.The polarization of alveolar macrophages was detected by flow cytometry.Data were analyzed using SPSS 22.0 software.Unpaired Student's t-test was used to analyze the differences between the two groups,and P<0.05 was considered statistically significant.Results Compared with the control group,the levels of multiple cytokines such as IL-12 p70 and MIP-2 in the plasma of mice in the 8-oxo-Guo group were significantly upregulated,while IL-33 was significantly downregulated.GO enrichment analysis showed that the changed cytokines were mainly enriched in functions such as immune effector regulation and were similar to the cellular response to lipopolysaccharide.In the detection of alveolar macrophages,the proportion of CD86^(+)CD206^(-)cells and the fluorescence intensity of CD86^(+)in alveolar macrophages of mice in the 8-oxo-Guo group increased,indicating that 8-oxo-Guo could induce the polarization of alveolar macrophages towards the M1 type.Conclusion Based on the mouse model,this study demonstrated that 8-oxo-Guo induced an up-regulation of plasma cytokine production and a pro-inflammatory shift of alveolar macrophages in mice,suggesting that

关 键 词：8-氧化鸟苷 细胞因子 肺泡巨噬细胞 肺免疫炎症 

分 类 号：R563[医药卫生—呼吸系统]