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

作　　者：刘宇涵 王莹莹 王钰铖 郭磊[1] 鞠瑞[1] 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)

机构地区：[1]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

出　　处：《基础医学与临床》2025年第5期616-621,共6页Basic and Clinical Medicine

基　　金：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)。

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。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.

关 键 词：巨噬细胞 脓毒症 Mcart1 炎性反应 

分 类 号：R392.12[医药卫生—免疫学]