葛花提取物通过激活PPARγ上调ABCA1的表达而抑制THP-1源性泡沫细胞形成  

Pueraria Lobata Flowers Extract inhibits THP-1-derived foam cell formation by activating PPARγ to upregulate the expression of ABCA1

作　　者：朱容蓉 陈梦娇 赵真旺 刘嘉怡 吴剑锋 王宇菲 张敏[1] ZHU Rongrong;CHEN Mengjiao;ZHAO Zhenwang;LIU Jiayi;WU Jianfeng;WANG Yufei;ZHANG Min(Institute of Cardiovascular Disease,University of South China&Key Laboratory for Arteriosclerology of Hunan Province&Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease&Department of Bioinformatics and Medical Big Data,University of South China,Hengyang,Hunan 421001,China;Medical Department of Basic Med-ical College,Hubei University of Arts and Science,Xiangyang,Hubei 441053,China;School of Public Health&Labora-tory Medicine,Hunan University of Medicine,Huaihua,Hunan 418000,China;Department of Cardiology,Second Affili-ated Hospital of University of South Hunan China)

机构地区：[1]南华大学心血管疾病研究所,动脉硬化学湖南省重点实验室,湖南省动脉硬化性疾病国际科技创新合作基地,南华大学生物信息与医学大数据教研室,湖南省衡阳市421001 [2]湖北文明学院医学部基础医学院,湖北省襄阳市441053 [3]湖南医药学院公共卫生与检验医学院,湖南省怀化市418000 [4]南华大学附属第二医院心血管内科,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2024年第5期395-401,共7页Chinese Journal of Arteriosclerosis

基　　金：湖南省教育厅科学研究项目(19B490);湖北省自然科学基金青年项目(2023AFB043、2021JJ40485);大学生创新创业项目(S202112214008)。

摘　　要：[目的]探寻葛花提取物(PFE)对巨噬细胞源性泡沫细胞脂质蓄积的影响。[方法]通过MTT法筛选PFE对THP-1源性泡沫细胞的作用浓度,采用油红O染色和胆固醇检测试剂盒检测细胞内脂质蓄积情况,采用胆固醇流出试剂盒检测细胞的胆固醇流出水平,使用RT-qPCR和Western blot检测mRNA和蛋白表达。[结果]PFE显著降低THP-1源性泡沫细胞内的脂质蓄积。PFE不影响CD36、清道夫受体AⅠ(SR-AⅠ)、固醇调节元件结合蛋白2(SREBP2)及3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)的mRNA表达,但能上调ATP结合盒转运体A1(ABCA1)的mRNA和蛋白表达水平(P<0.05),促进巨噬细胞源性泡沫细胞胆固醇流出(P<0.01)。PFE可以激活过氧化物酶体增殖物激活受体γ(PPARγ)的活性(P<0.01)及上调其mRNA和蛋白表达水平(P<0.05)。与PFE对照组相比,加入GW9662处理后PPARγ和ABCA1的蛋白表达水平均下降(P<0.01),胆固醇流出水平降低(P<0.01)。[结论]PFE可显著改善THP-1源性泡沫细胞内的脂质蓄积,通过PPARγ上调ABCA1表达及其介导的胆固醇流出抑制泡沫细胞形成。Aim To explore the effect of Pueraria Lobata Flowers Extract(PFE)on lipid accumulation in mac-rophage-derived foam cells.Methods The concentration of PFE in THP-1-derived foam cells was screened by MTT,intracellular lipid accumulation was detected by oil red O staining and cholesterol detection kit,intracellular cholesterol ef-flux levels were detected by cholesterol efflux assay kit,RT-qPCR and Western blot were used to analyze mRNA and pro-tein expression.Results PFE significantly reduced lipid accumulation in THP-1-derived foam cells.PFE did not affect the mRNA expression of CD36,scavenger receptor-AⅠ(SR-AⅠ),sterol regulatory element-binding protein 2(SREBP2),3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),but it could upregulate the mRNA and protein expres-sion levels of ATP-binding cassette transporter A1(ABCA1)(P<0.05),and promote the intracellular cholesterol efflux of macrophage-derived foam cells(P<0.01).PFE could activate the activity of peroxisome proliferator-activated receptorγ(PPARγ)(P<0.01)and upregulate the mRNA and protein expression levels of PPARγ(P<0.05).Compared with the PFE control group,the expression of PPARγand ABCA1 proteins decreased and cholesterol efflux decreased after GW9662 treatment(all P<0.01).Conclusion PFE could significantly prevent the lipid accumulation in THP-1-derived foam cells and inhibit the formation of foam cells by upregulating ABCA1 expression and cholesterol efflux mediated by PPARγ.

关 键 词：葛花提取物 泡沫细胞 ATP结合盒转运体A1 过氧化物酶体增殖物激活受体Γ 

分 类 号：R363.2[医药卫生—病理学] R5[医药卫生—基础医学]