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OALib Journal期刊
ISSN: 2333-9721
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化合物e0869体外抗动脉粥样硬化的活性研究
, PP. 440-446
Keywords: 4-甲磺酰甲基苯甲酸-1-(3,4-二甲基苯基)-1-丙酮-2-酯,atp结合盒转运体,清道夫受体b型i,动脉粥样硬化
Abstract:
atp结合盒转运体a1(atp-bindingcassettetransportera1,abca1)和清道夫受体b型i(scavengerreceptorclassbtypei,sr-bi/cla-1)是胆固醇逆转运过程中的重要蛋白.abca1和sr-bi/cla-1的高表达能降低动脉粥样硬化的危险性.因此,本研究利用前期已建立的人abca1和cla-1表达上调剂筛选模型,对20000个化合物进行筛选,获得能上调abca1和cla-1表达的化合物e0869[4-甲磺酰甲基苯甲酸-1-(3,4-二甲基苯基)-1-丙酮-2-酯],其上调活性分别为160%和175%,ec50值分别为3.79和1.42μmol·l-1;进一步研究发现,活性化合物e0869能上调肝细胞hepg2以及巨噬细胞raw264.7中abca1、sr-bi/cla-1以及abcg1的mrna和蛋白水平,但不影响fas、srebp-1c、cd36的表达;e0869能使泡沫化巨噬细胞raw264.7胞内脂滴量明显减少,并能增加其胆固醇的流出.因此,化合物e0869能够上调abca1和cla-1活性,并且具有较好的体外抗动脉粥样硬化效果.
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