文章摘要
刘 雪,马春梅,王冰微,杨 硕.炎症小体AIM2在小鼠肥胖发生过程中的作用和机制研究[J].南京医科大学学报,2021,(3):317~323
炎症小体AIM2在小鼠肥胖发生过程中的作用和机制研究
The role and mechanism of AIM2 in the development of obesity in mice
投稿时间:2020-04-21  
DOI:10.7655/NYDXBNS20210302
中文关键词: AIM2  肥胖  巨噬细胞极化
英文关键词: AIM2  obesity  macrophage polarization
基金项目:南京医科大学科技发展基金(NMUB2019007)
作者单位
刘 雪 南京医科大学免疫学系江苏 南京 211166 
马春梅 南京医科大学免疫学系江苏 南京 211166 
王冰微 南京中医药大学药理学系江苏 南京 210023 
杨 硕 南京医科大学免疫学系江苏 南京 211166 
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中文摘要:
      目的:明确黑素瘤缺乏因子2(absent in melanoma 2,AIM2)在小鼠肥胖发生过程中的作用,探索其中发挥作用的细胞及其调控肥胖发生的作用机制。方法:分别对AIM2敲除小鼠和AIM2fl/flCx3cr1?Cre小鼠进行60%高脂饲料喂养建造肥胖模型,每周称重小鼠监测其体重变化,HE染色分析脂肪组织结构。葡萄糖耐受和胰岛素敏感性实验分析AIM2是否影响胰岛素抵抗。流式细胞分析巨噬细胞分型变化,荧光定量PCR法检测促炎细胞因子和抑炎细胞因子的表达变化。结果:在高脂诱导的肥胖小鼠中,AIM2表达显著下调,AIM2基因敲除小鼠体重增加,脂肪细胞显著大于野生型小鼠,并且AIM2基因敲除小鼠对胰岛素的敏感性更差。特异性地在巨噬细胞中敲除小鼠AIM2基因的AIM2fl/flCx3cr1?Cre小鼠与上述AIM2基因敲除小鼠的结果一致。在体外对骨髓来源的巨噬细胞给予特异性的分型刺激,结果证实AIM2促进巨噬细胞向M1型巨噬细胞极化。结论:AIM2在小鼠肥胖发生过程中起保护作用,AIM2主要通过调控巨噬细胞极化来调节肥胖的发生。
英文摘要:
      Objective:This study aims to identify the role of AIM2(absent in melanoma 2)in the development of obesity in mice,explore the functioning cells and the regulation mechanism of obesity. Methods:AIM2 knockout mice and AIM2fl/fl Cx3cr1?Cre mice were given 60% high?fat food to induce obesity. The body weight changes of mice was monitored every week. HE staining was used to analyze the adipose tissue structure. Glucose tolerance and insulin sensitivity test was used to analyze the role of AIM2 in insulin resistance. Flow cytometry analysis was used to detect the changes of macrophage typing,and fluorescence quantitative PCR method was used to detect the expression of pro?inflammatory cytokines and anti?inflammatory cytokines. Results:In high?fat?induced obese mice,AIM2 was significantly down?regulated. The body weight of AIM2 knockout mice exhibit much higher than WT mice,and AIM2 knockout mice were less sensitive to insulin. What is more,the results of specific AIM2 knockout mice in macrophages AIM2fl/fl Cx3cr1?Cre were consistent with the full AIM2 knockout mice. In addition,bone marrow derived macrophages stimulated results in vitro confirmed that AIM2 promoted the polarization of macrophages into M1 type macrophages. Conclusion: AIM2 plays a protective role in the development of obesity in mice. It mainly regulates the occurrence of obesity by regulating the polarization of macrophages.
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