敲除Mcart1加重脓毒症模型小鼠巨噬细胞炎性反应水平

doi:10.16352/j.issn.1001-6325.2025.05.0616

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (5): 616-621.doi: 10.16352/j.issn.1001-6325.2025.05.0616

敲除Mcart1加重脓毒症模型小鼠巨噬细胞炎性反应水平

刘宇涵, 王莹莹, 王钰铖, 郭磊, 鞠瑞^*

中国医学科学院基础医学研究所北京协和医学院基础学院药理系,北京 100005

收稿日期:2025-01-02 修回日期:2025-02-20 出版日期:2025-05-05 发布日期:2025-04-23
通讯作者: ^* jurui1984@163.com
基金资助:
呼吸和共病全国重点实验室开放课题基金(2060204);科技创新2030 -“脑科学与类脑研究”重大项目 2021年度定向委托项目(2021ZD0201100); “人脑组织资源库及地区脑库协作网络平台”课题1(2021ZD0201101)

Mcart1 knockout enhances the level of macrophage inflammatory response in sepsis model mice

LIU Yuhan, WANG Yingying, WANG Yucheng, GUO Lei, JU Rui^*

Department of Pharmacology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2025-01-02 Revised:2025-02-20 Online:2025-05-05 Published:2025-04-23
Contact: ^* jurui1984@163.com

摘要/Abstract

摘要： 目的通过体内外模型检测Mcart1敲除对巨噬细胞急性炎性反应的影响。方法使用脂多糖(LPS),在Mcart1敲除的小鼠上构建小鼠脓毒症模型并检测生存期LPS致炎小鼠骨髓来源的巨噬细胞(BMDM)培养于DMEM高糖培养基中,采用RT-qPCR检测BMDM在LPS刺激后M1和M2相关细胞因子的mRNA水平;采用ELISA检测脓毒症小鼠血清中炎性反应相关介质的表达水平。结果相比野生型小鼠(Mcart1^flox/flox),Mcart1敲除小鼠(Mcart1^Lyz2-Cre)的脓毒症生存期显著缩短(P＜0.001),Mcart1^Lyz2-Cre鼠的BMDM细胞在LPS致炎后M1相关介质的mRNA水平上调(P＜0.05),M2相关介质的mRNA水平下调(P＜0.05),脓毒症Mcart1^Lyz2-Cre小鼠血清中M1相关介质表达上调(P＜0.01)。结论 Mcart1敲除可显著升高巨噬细胞的炎性反应水平,并加重小鼠的病理症状。

关键词: 巨噬细胞, 脓毒症, Mcart1, 炎性反应

Abstract: Objective To investigate the effect of Mcart1 knockout on acute inflammation of macrophages in vitro and in vivo. Methods The Mcart1 knockout mice were used to establish a sepsis model induced by lipopolysaccharide(LPS), and the survival period was measured. Bone marrow derived macrophages(BMDM) of LPS-induced inflammation mice were cultured in DMEM high-glucose medium. The mRNA levels of M1 and M2 related cytokines of BMDM after LPS stimulation were detected by RT-qPCR. The expression level of inflammation-related cytokines in serum of sepsis mice was detected by ELISA. Results Compared with wild type mice(Mcart1^flox/flox), the survival time length of sepsis in Mcart1 knockout mice(Mcart1^Lyz2-Cre)was significantly shortened(P＜0.001). After inflammation, the mRNA level of M1-related cytokines was up-regulated in BMDM cells of Mcart1^Lyz2-Cre mice(P＜0.05); The mRNA level of M1-related cytokines was down-regulated(P＜0.05); The expression of M1-related mediators in serum of sepsis Mcart1^Lyz2-Cre mice was up-regulated(P＜0.01). Conclusions Mcart1 knockout can significantly raise the inflammatory response of macrophages and aggravate the pathological symptoms of sepsis mice.

Key words: macrophages, sepsis, Mcart1, inflammation

中图分类号:

R392.12

刘宇涵, 王莹莹, 王钰铖, 郭磊, 鞠瑞. 敲除Mcart1加重脓毒症模型小鼠巨噬细胞炎性反应水平[J]. 基础医学与临床, 2025, 45(5): 616-621.

LIU Yuhan, WANG Yingying, WANG Yucheng, GUO Lei, JU Rui. Mcart1 knockout enhances the level of macrophage inflammatory response in sepsis model mice[J]. Basic & Clinical Medicine, 2025, 45(5): 616-621.

参考文献

[1]Hotchkiss RS, Tinsley KW, Karl IE. Role of apoptotic cell death in sepsis[J]. Scand J Infect Dis, 2003, 35:585-592.
[2]Dauphinee S, Karsan A. Lipopolysaccharide signaling in endothelial cells[J].Lab Invest, 2006,86:9-22.
[3]Yeung ST, Ovando LJ, Russo AJ, et al. CD169⁺ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis[J]. Cell Rep, 2023, 42:112171.doi: 10.1016/j.celrep.2023.112171.
[4]Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets[J]. Nat Rev Immunol, 2011, 11:723-737.
[5]Luongo TS, Eller JM, Lu MJ, et al. SLC25A51 is a mammalian mitochondrial NAD⁺ transporter[J]. Nature, 2020, 588:174-179.
[6]Wang Q, Hu J, Han G, et al. PTIP governs NAD⁺ metabolism by regulating CD38 expression to drive macrophage inflammation[J]. Cell Rep, 2022, 38:110603. doi: 10.1016/j.celrep.2022.110603.
[7]张迪雅,李云帆,郭泓江,等. 胶质瘤条件培养基促进巨噬细胞糖酵解及表型转化[J]. 基础医学与临床, 2024, 44:599-605.
[8]Jiao Y, Wai Tong CS, Rainer TH. An appraisal of studies using mouse models to assist the biomarker discovery for sepsis prognosis[J]. Heliyon, 2023,9:e17770. doi: 10.1016/j.heliyon.2023.e17770.
[9]Langston PK, Nambu A, Jung J, et al. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses[J]. Nat Immunol, 2019, 20:1186-1195.
[10]赵永晶,仇佳星,张迪雅,等. 稳定敲除Mcart-1下调RAW264.7巨噬细胞增殖能力和氧化磷酸化水平[J]. 基础医学与临床, 2023, 43:568-575.
[11]Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines[J]. Immunity, 2014, 41:14-20.
[12]Mills CD, Kincaid K, Alt JM, et al. M-1/M-2 macrophages and the Th1/Th2 paradigm[J]. J Immunol, 2000, 164:66-73.
[13]Seim GL, Britt EC, John SV, et al. Two-stage metabolic remodelling in macrophages in response to lipopolysaccharide and interferon-γ stimulation[J].Nat Metab, 2019, 1:731-742.
[14]Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity[J]. Adv Immunol, 2013, 120:163-184.

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敲除Mcart1加重脓毒症模型小鼠巨噬细胞炎性反应水平

Mcart1 knockout enhances the level of macrophage inflammatory response in sepsis model mice

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