中国药理学通报2023，Vol.39Issue(12)：2266-2273,8.DOI:10.12360/CPB202305009
野黄芩素通过促进胆固醇外流途径抑制巨噬细胞泡沫化的作用机制
Mechanism of scutellarein inhibiting foaming of macrophages by promoting cholesterol efflux pathway
摘要
Abstract
Aim To investigate the effects of scutella-rein on the macrophage foam cell formation and choles-terol efflux,and the underlying mechanism.Methods THP-1 cells were differentiated with PMA,and the cell viability was detected by MTT assays.The effects of scutellarein on the cholesterol efflux and macrophage foam cell formation were evaluated by using NBD-la-beled cholesterol and the cholesterol detection kit.The effects of scutellarein on the activation of PPARγ-LXRα-ABCA1 signaling pathway were determined by molecular docking,ELISA,dual-luciferase reporter and Western blot.The effects of PPARγ knowdown on scutellarein-induced cholesterol efflux and inhibiting macrophage foaming were analyzed by siRNA interfer-ence.Results Scutellarein dose-dependently inhibi-ted oxLDL-induced cholesterol accumulation,acceler-ated cholesterol efflux and significantly increased the protein expression of LXRα and ABCA1.At the same time,scutellarein could bind PPARγ and initiate its downstream LXRα-ABCA 1 signaling pathway.In addi-tion,gene silencing of PPARγ not only significantly in-hibited scutellarein-induced LXRα-ABCA1 signaling pathway and cholesterol efflux,but also reversed the inhibitory effect of scutellarein on macrophage foaming.Conclusions Scutellarein could promote the choles-terol efflux by activating PPARγ and initiating the downstream LXR-ABCA1 signaling pathway,thereby prevent the macrophage foam cell formation.关键词
野黄芩素/动脉粥样硬化/氧化低密度脂蛋白/PPARγ/巨噬细胞泡沫化/胆固醇外流Key words
scutellarein/atherosclerosis/oxidized low density lipoprotein/PPARγ/macrophage foam cell for-mation/cholesterol efflux分类
医药卫生引用本文复制引用
吴若琳,黄裕鸿,王天琦,孙文龙,李敬达..野黄芩素通过促进胆固醇外流途径抑制巨噬细胞泡沫化的作用机制[J].中国药理学通报,2023,39(12):2266-2273,8.基金项目
国家自然科学青年科学基金资助项目(No 82004020) （No 82004020）
国家自然科学青年科学基金资助项目(No 81903878) （No 81903878）
