补骨脂酚通过抑制ERK1/2磷酸化并上调ABCA1表达减少巨噬细胞源性泡沫细胞形成  

Bakuchiol inhibits macrophage-derived foam cell formation by reducing ERK1/2 phosphorylation and upregulating ABCA1 expression

作　　者：王楊 周琴怡 王刚 唐朝克 WANG Yang;ZHOU Qinyi;WANG Gang;TANG Chaoke(Institute of Cardiovascular Disease&Key Laboratory for Arteriosclerology of Hunan Province&Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease,Hengyang Medical School,University of South China;Department of Cardiology,the Affiliated Nanhua Hospital,Hengyang Medical School,University of South China;Key Laboratory of Cardiovascular Diseases Multi-Omics and Artificial Intelligence,Hunan Province;Department of Cardiology,the First Affiliated Hospital,Hengyang Medical School,University of South China;Clinical Medical Research Center for Myocardial Injury,Hunan Province;Institute of Cardiovascular Diseases,the First Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang,Hunan 421001,China)

机构地区：[1]南华大学衡阳医学院心血管疾病研究所,湖南省动脉硬化学重点实验室,湖南省动脉硬化性疾病国际科技合作创新基地 [2]南华大学衡阳医学院附属南华医院心内科 [3]心脏疾病多组学与人工智能湖南省重点实验室 [4]南华大学衡阳医学院附属第一医院心内科 [5]湖南省心肌损伤临床医学研究中心 [6]南华大学衡阳医学院附属第一医院心血管疾病研究所,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2024年第9期763-770,共8页Chinese Journal of Arteriosclerosis

基　　金：湖南省教育厅重点项目(21A0275);湖南省卫生健康委一般项目(202103011860);创新平台与人才计划(2023TP1047);湖南省自然科学基金面上项目(2023JJ30547和2022JJ30540);湖南省卫生健康委重大专项(W20241008);南华大学附属第一医院4310计划(20214310NHYCG03)。

摘　　要：[目的]探讨补骨脂酚(BAK)对巨噬细胞源性泡沫细胞脂质蓄积的影响及机制。[方法]MTT筛选BAK对泡沫细胞药物毒性浓度;油红O染色、NBD胆固醇、Dil-ox-LDL检测泡沫细胞内脂质蓄积情况;使用RT-qPCR和Western blot检测mRNA和蛋白表达。[结果]BAK可以促进胆固醇流出并减少泡沫细胞内脂质蓄积。BAK可以上调三磷酸腺苷结合盒转运体A1(ABCA1)的mRNA和蛋白表达水平,同时可下调细胞外信号调节激酶1/2(ERK1/2)磷酸化水平。使用ERK1/2激动剂Ro 67-7476处理发现,与BAK处理组相比,加入Ro 67-7476处理后ABCA1蛋白表达下降。[结论]BAK通过抑制ERK1/2的磷酸化,上调ABCA1的表达并促进胆固醇的流出,减少泡沫细胞中的脂质蓄积,从而抑制泡沫细胞的形成。Aim To investigate the impact of bakuchiol(BAK)on lipid accumulation in macrophage-derived foam cell and explore the underlying mechanisms.Methods MTT assay was used to determine the non-toxic concentration of BAK on foam cell.Oil red O staining,NBD cholesterol,and Dil-ox-LDL were used to assess lipid accumulation in foam cell.RT-qPCR and Western blot were utilized to measure mRNA and protein expression,respectively.Results BAK promoted cholesterol effux and reduced lipid accumulation in foam cell.BAK upregulated the mRNA and protein expression levels of ATP-binding cassette transporter A1(ABCA1)and concurrently downregulated the phosphoryl-ation levels of extracellular signal-regulated kinase 1/2(ERK1/2).Treatment with the ERK1/2 activator Ro 67-7476 re-sulted in decreased ABCA1 protein expression compared with the BAK-treated group.Conclusion BAK reduced lipid accumulation in foam cell by inhibiting ERK1/2 phosphorylation,upregulating ABCA1 expression,and promoting choles-terol efflux,thereby suppressing foam cell formation.

关 键 词：补骨脂酚 泡沫细胞 三磷酸腺苷结合盒转运体A1 细胞外信号调节激酶1/2 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]