表松脂醇抑制巨噬细胞泡沫化的作用及潜在机制研究  

Inhibition of epipinoresinol on macrophage foam and potential mechanisms

作　　者：王帅[1] 刘明玥[1,2] 张雪[1,2] 李欣[1] 郭鹏[1] 吴崇明[1] 

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所药理毒理中心,北京100193 [2]哈尔滨商业大学生命科学与环境科学研究中心,黑龙江哈尔滨150076

出　　处：《中草药》2015年第18期2737-2742,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81001437);北京市自然科学基金资助项目(7102111)

摘　　要：目的探究表松脂醇在抗巨噬细胞泡沫化方面的作用及潜在机制。方法采用倒置显微镜拍照和用酶标仪检测吸光度等方法,评价表松脂醇对泡沫细胞形成的抑制作用。采用荧光检测法检测胆固醇流入及流出情况,用实时荧光定量PCR(RT-PCR)检测流出、流入相关基因的表达情况。结果表松脂醇能够显著抑制RAW264.7巨噬细胞由氧化低密度脂蛋白(ox-LDL)诱导的胆固醇累积,能够显著增强由高密度脂蛋白(HDL)介导的胆固醇流出,同时还能够显著抑制胆固醇的流入。RT-PCR结果表明,表松脂醇能够上调过氧化物增殖激活受体γ(PPARγ)、肝X受体α(LXRα)、ATP结合盒转运子A1(ABCA1)和ATP结合盒转运子G1(ABCG1)基因m RNA的水平,下调清道夫受体A1(SR-A1)和A2(SR-A2)基因m RNA的水平。结论表松脂醇是一种新的泡沫细胞形成抑制剂,其作用可能是通过上调PPARγ-LXRα-ABCA1/ABCG1通路和下调SR-A1、SR-A2实现的,其可能在防治动脉粥样硬化方面具有潜在的作用。Objective To clarify the potential inhibitive effect of epipinoresinol on macrophage foam and potential mechanisms. Methods The inhibition of epipinoresinol on foam cell formation after stained with oil red O was assessed by Image-Pro Plus and Microplate Reader, and the effect on cholesterol efflux and influx was tested by fluorescence detection to obtain cholesterol inflows-time curve and outflow rate. Additionally the cholesterol flow-associated genes expression was checked by real-time PCR（RT-PCR）. Results Epipinoresinol dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol（ox-LDL） in RAW264.7 cells. Treatment with epipinoresinol significantly enhanced the cholesterol efflux mediated by high-density lipoprotein（HDL） and substantially inhibited the cholesterol influx. RT-PCR showed that epipinoresinol significantly increased the m RNA levels of PPARγ, LXRα, ABCA1, and ABCG1, decreased those of SR-A1 and SR-A2. Conclusion Epipinoresinol is a new inhibitor on foam cell formation that may stimulate the cholesterol efflux through up-regulating the PPARγ-LXRα-ABCA1/ABCG1 pathway and prevent cholesterol influx through down-regulating SR-A1 and SR-A2, which may be useful on atherosclerosis treatment.

关 键 词：表松脂醇 动脉粥样硬化 泡沫细胞 胆固醇流入 胆固醇流出 巨噬细胞 

分 类 号：R285.5[医药卫生—中药学]