中国药理学通报2026，Vol.42Issue(9)：1636-1644,9.DOI:10.12360/CPB202510083
CKLF1介导脂质过载卒中模型的内皮细胞线粒体损伤与血管重塑障碍
CKLF1 mediates endothelial mitochondrial damage and impairs revascularization in a stroke model with lipid overload
摘要
Abstract
Aim Post-stroke vascular remodeling is fundamental for neurological recovery but is often im-paired in obese patients through poorly understood mo-lecular mechanisms.This study aims to elucidate the pathological role of chemokine-like factor 1(CKLF1)in impaired post-stroke revascularization under lipid overload conditions,to investigate the underlying mito-chondrial mechanisms,and to evaluate the potential of targeted intervention.Methods We established a mu-rine model using a high-fat diet combined with distal middle cerebral artery occlusion(dMCAO)and an in vitro model of endothelial lipid overload induced by palmitic acid(PA).A comprehensive approach,in-cluding behavioral assessments,two-photon in vivo im-aging,transcriptomic sequencing,and mitochondrial function analysis,was used to investigate the role of CKLF1.A neutralizing antibody against CKLF1 was used for interventional validation.Results Lipid over-load significantly exacerbated sensorimotor deficits and suppressed peri-infarct revascularization in dMCAO mice,accompanied by an abnormal upregula-tion of CKLF1 in brain tissue.Mechanistically,CKLF1 led to severe mitochondrial network fragmenta-tion,dissipation of mitochondrial membrane potential,and bursts of oxidative stress in endothelial cells.We identified a pathological crosstalk between CKLF1 and the PINK1/PRKN-mediated mitophagy pathway,lead-ing to aberrant expression of related proteins(PINK1,PRKN,SQSTM1).Application of the CKLF1 neutral-izing antibody effectively reversed this mitochondrial dysfunction and impairment of revascularization.Con-clusions CKLF1 is a key pathogenic factor that medi-ates the lipid overload-induced exacerbation of post-stroke revascularization and neurological recovery.It exerts its damaging effects by disrupting mitochondrial homeostasis in endothelial cells,suggesting that CKLF1 may be an effective therapeutic target for pro-moting stroke recovery in the obese population.关键词
趋化素样因子1/脂质过载/脑卒中/脑微血管内皮细胞/血管重塑/线粒体稳态Key words
chemokine-like factor 1/lipid overload/stroke/brain microvascular endothelial cells/revascu-larization/mitochondrial homeostasis分类
医药卫生引用本文复制引用
赵亚娴,胡凯超,贺文彬,楚世峰,张钊..CKLF1介导脂质过载卒中模型的内皮细胞线粒体损伤与血管重塑障碍[J].中国药理学通报,2026,42(9):1636-1644,9.基金项目
国家自然科学基金资助项目(No U21A20410,82374060) （No U21A20410,82374060）
