中国实验动物学报2026，Vol.34Issue(4)：544-552,9.DOI:10.3969/j.issn.1005-4847.2026.04.007
巨噬细胞特异性敲除KLF2对ApoE-/-小鼠动脉粥样硬化斑块的影响
Impact of macrophage-specific KLF2 deficiency on atherosclerosis progression in ApoE-/-mice
摘要
Abstract
Objective To establish a double-knockout mouse model of apolipoprotein E(ApoE)and macrophage-specific Krüppel-like factor 2(KLF2)and to investigate the role of macrophage KLF2 in the progression of atherosclerosis.Methods KLF2flox/flox/Lyz2-Cre+mice were crossed with ApoE-/-mice over multiple generations to generate KLF2flox/flox/Lyz2-Cre+/ApoE-/-mice.KLF2 knockout efficiency at the mRNA and protein levels was verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR)and Western Blot analysis.Atherosclerosis was induced by feeding mice a high-fat diet.Plaque formation and lipid metabolism were compared between the model group(KLF2flox/flox/Lyz2-Cre+/ApoE-/-)and the control group(KLF2flox/flox/ApoE-/-).Results A macrophage-specific KLF2 and ApoE double-knockout mouse model(KLF2flox/flox/Lyz2-Cre+/ApoE-/-)was successfully established.Histopathological analysis demonstrated significantly increased aortic root plaque area and lipid accumulation in the model group compared with controls.In addition,the model group exhibited markedly elevated serum total cholesterol,triglycerides,and low-density lipoprotein cholesterol levels,as well as increased hepatic lipid accumulation.Macrophage infiltration within aortic plaques was also significantly higher in the model group.Conclusions Macrophage-specific deletion of KLF2 accelerates atherosclerotic plaque progression,potentially through dysregulation of lipid metabolism and enhanced macrophage adhesion and migration.This model provides a valuable experimental platform for further elucidating the role of macrophage KLF2 in atherosclerosis and related cardiovascular diseases.关键词
Krüppel样因子2/巨噬细胞/特异性敲除小鼠/动脉粥样硬化斑块/脂质代谢Key words
Krüppel-like factor 2/macrophages/specific knockout mice/atherosclerosis progression/lipid metabolism分类
生物科学引用本文复制引用
王新洲,雷泽昊,刘珊珊,秦楠,于晓芳,吴鸿..巨噬细胞特异性敲除KLF2对ApoE-/-小鼠动脉粥样硬化斑块的影响[J].中国实验动物学报,2026,34(4):544-552,9.基金项目
河南省科技攻关项目(242102310447),河南省"双一流"创建学科中医学科学研究专项(HSRP-DFCTCM-2023-7-20).Funded by the Henan Provincial Science and Technology Research Project(242102310447),Henan Province"Double First-Class"Construction Project-Special Program for Scientific Research in Traditional Chinese Medicine(HSRP-DFCTCM-2023-7-20). （242102310447）
