柯里拉京调节巨噬细胞胆固醇代谢的作用及其机制  

Effect of corilagin on cholesterol metabolism in macrophages and its mechanism

作　　者：邓欣 孟达 吴静宜 姜丙通 杨轶洋 张雅琼 赵毅 黄丰 车彦云 DENG Xin;MENG Da;WU Jing-yi;JIANG Bing-tong;YANG Yi-yang;ZHANG Ya-qiong;ZHAO Yi;HUANG Feng;CHE Yan-yun(College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China;School of Environmented Science and Engineering,Taiyuan Institute of Technology,Taiyuan 030008,China)

机构地区：[1]云南中医药大学中药学院,云南昆明650500 [2]太原工业学院环境与安全工程系,山西太原030008

出　　处：《中国药理学通报》2023年第9期1696-1704,共9页Chinese Pharmacological Bulletin

基　　金：云南省科技厅-云南中医药大学应用基础联合研究专项项目重点项目(No 2019FF002(-012));云南省科技厅-云南中医药大学应用基础联合研究专项项目面上项目(No 202101AZ070001-212)。

摘　　要：目的探究柯里拉京(corilagin,Cor)调节巨噬细胞胆固醇代谢的作用及机制。方法采用分子对接技术,预测Cor调节胆固醇代谢的蛋白靶点。结合80 mg·L^(-1)氧化修饰型低密度脂蛋白(oxidized low-density lipoproteins,ox-LDL)诱导建立的RAW264.7巨噬细胞泡沫模型评价其活性;采用实时聚合酶链式反应和免疫印迹方法检测胆固醇代谢相关基因和蛋白表达;并通过高脂饮食诱导ApoE-/-小鼠动脉粥样硬化(atherosclerosis,AS)模型研究其活性及其机制。结果Cor与胆固醇代谢相关的A类清道夫受体(class A scavenger receptor,SRA)和CD36以及过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)和细胞膜上的ATP结合盒转运体G1(ATP binding cassette transporter G1,ABCG1)蛋白能形成氢键和疏水相互作用。细胞实验表明,Cor(60、120和240μmol·L^(-1))降低巨噬细胞内TC的含量,下调SRA的基因和蛋白表达,下调CD36的基因表达,并上调了ABCA1和ABCG1的基因和蛋白表达。动物实验表明,Cor(15、30和60 mg·kg-1)降低小鼠血清中的TMAO含量,减少主动脉根部的斑块形成,降低了主动脉根部斑块中CD36、SRA的荧光蛋白表达水平。结论Cor能够通过调节CD36、SRA、ABCA1和ABCG1介导的胆固醇代谢,抑制巨噬细胞泡沫化,发挥抗AS作用。Aim To elucidate the effect of corilagin(Cor)on cholesterol metabolism in macrophages and the underlying mechanism.Methods Molecular docking was applied to predict the protein target of Cor on cellular cholesterol metabolism.The RAW264.7 macrophage foam model induced by 80 mg·L^(-1)oxidized low density lipoprotein(ox-LDL)was established to evaluate the activity of Cor on lowering-cholesterol.The expression of genes and proteins related with cholesterol metabolism were detected by q-PCR and Western blotting,respectively.Then the activity of Cor on lipid metabolism was validated in ApoE-/-mice fed with high-fat-diet.Results Cor and Class A Scavenger receptor(SRA),CD36,peroxisome proliferator-activated receptorγ(PPARγ),ATP binding cassette transporter G1(ABCG1),which associated with cholesterol metabolism,could form hydrogen bonds and hydrophobic interactions.Cell experiments showed that Cor(60,120 and 240μmol·L^(-1))significantly decreased TC content in macrophages,Cor could down-regulate SRA and CD36 gene expression,SRA protein expression,up-regulate the expression of ABCA1 and ABCG1 genes.Animal experiments demonstrated that Cor(15,30 and 60 mg·kg-1)could decrease the serum TMAO content,the plaque area and formation of foam cells in the aortic root,the expression levels of CD36 and SRA fluorescent proteins in aortic root plaques.Conclusions Cor could inhibit the formation of macrophage foam cells through the regulation of cholesterol metabolism mediated by CD36,SRA,ABCA1 and ABCG1 to cure the AS.

关 键 词：柯里拉京 巨噬细胞 胆固醇代谢 基因表达 蛋白表达 动脉粥样硬化 

分 类 号：R-332[医药卫生] R282.71R329.24R344.81R543.5