摘要
目的探讨阿托伐他汀钙是否通过调节PPARγ和NF-κB活性来抑制Ox-LDL诱导的THP-1巨噬细胞泡沫化形成。方法THP-1巨噬细胞与10、20、40μmol/L阿托伐他汀钙分别预孵育2 h,PBS洗2次,然后与60μg/ml ox-LDL共孵育48 h后,通过酶荧光法检测细胞胆固醇酯与总胆固醇比值,油红O染色观察细胞胞浆内脂质蓄积情况,Western blot分析清道夫受体CD36、SRA的表达,p-iκB和PPARγ的表达,以及ATP结合盒转运蛋白A1(ABCA1)的表达变化。用荧光探针DIL标记ox-LDL的方法,观察阿托伐他汀钙对THP-1巨噬细胞结合ox-LDL能力的影响。结果阿托伐他汀钙浓度依赖性降低THP-1巨噬细胞脂质蓄积和抑制清道夫受体CD36和SRA的表达,同时上调ABCA1表达,并减弱PPARγ和p-iκB活性(P<0.05)。荧光探针DIL标记ox-LDL的方法显示阿托伐他汀钙浓度依赖性降低THP-1巨噬细胞结合ox-LDL能力(P<0.05)。结论阿托伐他汀钙抗动脉硬化作用可能部分通过降低PPARγ和p-iκB活性来抑制脂质蓄积。
Objective To evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptorγ(PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40μmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 μg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγand p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL. Results Atorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγand p-iκB in ox-LDL-stimulated THP-1 macrophages (P〈0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P〈0.05). Conclusion Atorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2014年第6期896-900,共5页
Journal of Southern Medical University
关键词
阿托伐他汀钙
PPARΓ
NF-ΚB
THP-1细胞
细胞泡沫化
atorvastatin
peroxisome proliferator-activated receptor γ
nuclear factor-κB
THP-1 cells
macrophage-derivedfoam cells