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Mcart1基因敲除对小鼠巨噬细胞代谢及表型的影响

王莹莹 张楷晗 王钰铖 鞠瑞 郭磊

基础医学与临床2026,Vol.46Issue(6):807-814,8.
基础医学与临床2026,Vol.46Issue(6):807-814,8.DOI:10.16352/j.issn.1001-6325.2026.06.0807

Mcart1基因敲除对小鼠巨噬细胞代谢及表型的影响

Effects of Mcart1 gene knockout on metabolism and phenotype of mouse macrophages

王莹莹 1张楷晗 1王钰铖 1鞠瑞 1郭磊1

作者信息

  • 1. 中国医学科学院北京协和医学院 基础医学研究所 药理学系,北京 100005
  • 折叠

摘要

Abstract

Objective To investigate the effects of Mcart1 gene knockout on macrophage metabolism and phenotype.Methods Two types of bone marrow-derived macrophages(BMDMs)were obtained from Mcart1flox/flox and Mcart1Lyz2-cre mice.Basal respiration of both cell types was measured using a Seahorse analyzer.The activity of α-ketoglutarate dehydrogenase(OGDH)was assessed in Mcart1 stably knockout RAW264.7 cells(Mcart1-/--RAW264.7)and wild-type RAW264.7 cells(RAW264.7).The two types of BMDMs were induced into M1 mac-rophages using LPS,and whole-cell reactive oxygen species(ROS)levels were measured by flow cytometry,while dynamic expression of inflammatory mediators was monitored by qPCR.The two types of BMDMs were also induced into M2 macrophages using IL-4,and expression of M2 anti-inflammatory and tissue repair mediators was measured by qPCR,while protein levels of classical M2 activation markers were detected using Western blot.Results Com-pared with Mcart1flox/flox BMDMs,Mcart1 knockout significantly reduced basal respiration in BMDMs,and Mcart1 stable knockout decreased OGDH activity in macrophages(P<0.01).Mcart1 knockout significantly enhanced ROS production in M1 macrophages and upregulated early inflammatory mediators Il1b,Tnf,and Nos2(P<0.05),while having no significant effect on the expression of M2 anti-inflammatory and tissue repair mediators Arg1,Mrc1,Ret-nla,Cd163,Fn1,or classical activation proteins p-Stat6 and p-Stat3 in M2 macrophages.Conclusions Mcart1 knockout significantly suppresses basal respiration in macrophages,inhibits OGDH enzyme activity,increases oxi-dative stress and inflammatory mediator levels in M1 macrophages,and does not significantly affect functional medi-ator levels in M2 macrophages.

关键词

Mcart1/NAD+/活性氧/α-酮戊二酸脱氢酶/巨噬细胞极化

Key words

Mcart1/NAD+/reactive oxygen species/α-ketoglutarate dehydrogenase/macrophage polarization

分类

医药卫生

引用本文复制引用

王莹莹,张楷晗,王钰铖,鞠瑞,郭磊..Mcart1基因敲除对小鼠巨噬细胞代谢及表型的影响[J].基础医学与临床,2026,46(6):807-814,8.

基金项目

呼吸和共病全国重点实验室开放课题基金(2060204) (2060204)

中国医学科学院医药与健康科技创新工程探索项目(2025-I2M-TS-05) (2025-I2M-TS-05)

基础医学与临床

1001-6325

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