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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
引用本文:朱容蓉,陈梦娇,赵真旺,刘嘉怡,吴剑锋,王宇菲,张敏. 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[J]. 中国动脉硬化杂志, 2024, 32(5): 395-401
作者姓名:朱容蓉  陈梦娇  赵真旺  刘嘉怡  吴剑锋  王宇菲  张敏
作者单位: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;湖北文明学院医学部基础医学院,湖北省襄阳市 441053;湖南医药学院公共卫生与检验医学院,湖南省怀化市 418000;南华大学附属第二医院心血管内科,湖南省衡阳市 421001
基金项目: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。

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
收稿时间:2023-11-30
修稿时间:2024-02-08

Pueraria Lobata Flowers Extract inhibits THP-1-derived foam cell formation by activating PPARγ to upregulate the expression of ABCA1
ZHU Rongrong,CHEN Mengjiao,ZHAO Zhenwang,LIU Jiayi,WU Jianfeng,WANG Yufei,ZHANG Min. Pueraria Lobata Flowers Extract inhibits THP-1-derived foam cell formation by activating PPARγ to upregulate the expression of ABCA1[J]. Chinese Journal of Arteriosclerosis, 2024, 32(5): 395-401
Authors:ZHU Rongrong  CHEN Mengjiao  ZHAO Zhenwang  LIU Jiayi  WU Jianfeng  WANG Yufei  ZHANG Min
Affiliation: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 Medical College, Hubei University of Arts and Science, Xiangyang, Hubei 441053, China;School of Public Health & Laboratory Medicine, Hunan University of Medicine, Huaihua, Hunan 418000, China;Department of Cardiology, Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China
Abstract:Aim To explore the effect of Pueraria Lobata Flowers Extract (PFE) on lipid accumulation in macrophage-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 efflux levels were detected by cholesterol efflux assay kit, RT-qPCR and Western blot were used to analyze mRNA and protein 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 expression 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 receptor γ (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 PPARγ and 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.
Keywords:Pueraria Lobata Flowers Extract   foam cell   ATP-binding cassette transporter A1   peroxisome proliferator-activated receptor γ
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