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谭超, 张仪, 王子焱, 徐艺嘉, 李明笑, 张国民.姜黄素通过miR-125a-3p/S1PR3通路调控THP-1源性巨噬细胞泡沫化及胆固醇流出蛋白ABCA1/G1表达的研究[J].湖南中医药大学学报,2026,46(5):898-906[点击复制] |
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| 姜黄素通过miR-125a-3p/S1PR3通路调控THP-1源性巨噬细胞泡沫化及胆固醇流出蛋白ABCA1/G1表达的研究 |
| 谭超,张仪,王子焱,徐艺嘉,李明笑,张国民 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学中医学国内一流建设学科, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨姜黄素对人单核细胞白血病细胞（THP-1）源性巨噬细胞泡沫化及胆固醇流出蛋白三磷酸腺苷结合盒转运蛋白A1/G1（ABCA1/G1）表达的影响，及其对miR-125a-3p表达和鞘氨醇-1-磷酸受体3（S1PR3）蛋白水平的调控机制。方法 以THP-1源性巨噬细胞为研究对象，分为空白组、模型组、姜黄素组、miR-125a-3p抑制剂组、阳性药物组。除空白组外其余各组采用氧化低密度脂蛋白（ox-LDL）诱导THP-1源性巨噬细胞形成泡沫化模型。模型诱导成功后，空白组、模型组予以完全培养基培养，姜黄素组、miR-125a-3p抑制剂组、阳性药物组分别予以姜黄素、miR-125a-3p抑制剂、阿托伐他汀钙共培养。采用油红O染色观察细胞形态；酶法检测细胞内总胆固醇（TC）、胆固醇酯（CE）含量；流式细胞术检测细胞极化水平；RT-qPCR测定细胞内miR-125a-3p、S1PR3 mRNA的表达水平；Western blot检测S1PR3、ABCA1、ABCG1蛋白表达水平；ELISA检测炎症因子白细胞介素（IL）-6、IL-1β、肿瘤坏死因子-α（TNF-α）表达水平。结果 与空白组比较，模型组细胞内橘红色颗粒显著增加，泡沫细胞形成率升高（P<0.05）；TC、CE水平升高（P<0.05）；M1型巨噬细胞极化程度升高（P＜0.05）；IL-6、IL-1β、TNF-α水平升高（P<0.05）；miR-125a-3p、S1PR3 mRNA表达上调（P<0.05）；ABCA1、ABCG1蛋白表达降低（P<0.05）。与模型组比较，姜黄素组、miR-125a-3p抑制剂组及阳性药物组细胞内橘红色颗粒显著减少，泡沫细胞形成率降低（P<0.05）；TC、CE及胆固醇酯化率下降（P<0.05）；M2型巨噬细胞极化程度升高（P＜0.05）；miR-125a-3p、S1PR3 mRNA表达下调（P<0.05），ABCA1、ABCG1蛋白表达升高（P<0.05）。与模型组比较，姜黄素组、miR-125a-3p抑制剂组IL-6、IL-1β、TNF-α水平降低（P<0.05）。结论 姜黄素可有效抑制THP-1源性巨噬细胞泡沫化，其机制可能与下调miR-125a-3p表达、降低S1PR3过度表达，进而上调胆固醇流出蛋白ABCA1/G1水平有关。 |
| 关键词: 姜黄素|THP-1源性巨噬细胞|巨噬细胞|泡沫化|鞘氨醇-1-磷酸受体3|miR-125a-3p |
| DOI：10.3969/j.issn.1674-070X.2026.05.004 |
| 投稿时间：2025-10-30 |
| 基金项目:湖南省自然科学基金科卫联合项目（2022JJ70112）；第六批全国中医临床优秀人才研修项目（中医药青年拔尖人才培养项目）（国中医药人教函〔2025〕256号）；湖南省“十四五”中医药骨干人才项目[湘中医药〔2024〕3号（骨干人才）]。 |
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| Curcumin regulation of foam cell formation and cholesterol efflux proteins ABCA1/G1 expression in THP-1-derived macrophages via the miR-125a-3p/S1PR3 pathway |
| TAN Chao, ZHANG Yi, WANG Ziyan, XU Yijia, LI Mingxiao, ZHANG Guomin |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;The Domestic First-class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To explore the effects of curcumin on foam cell formation and the expression of cholesterol efflux proteins adenosine triphosphate-binding cassette transporter A1/G1 (ABCA1/G1) in human monocytic leukemia cell (THP-1)-derived macrophages, as well as its regulatory mechanisms on miR-125a-3p expression and sphingosine-1-phosphate receptor 3 (S1PR3) protein levels. Methods THP-1-derived macrophages were used as the research subject and divided into blank group, model group, curcumin group, miR-125a-3p inhibitor group, and positive drug group. Except for the blank group, all groups were induced with oxidized low-density lipoprotein (ox-LDL) to establish a foam cell model in THP-1-derived macrophages. After successful induction, the blank and model groups were cultured in complete medium, while the curcumin, miR-125a-3p inhibitor, and positive drug groups were co-cultured with curcumin, miR-125a-3p inhibitor, and atorvastatin calcium, respectively. Oil Red O staining was used to observe cell morphology; enzymatic methods were used to determine intracellular total cholesterol (TC) and cholesterol ester (CE) levels; flow cytometry was employed to assess macrophage polarization; RT-qPCR was applied to measure intracellular miR-125a-3p and S1PR3 mRNA expression levels; Western blot was used to test the protein expression levels of S1PR3, ABCA1, and ABCG1; and ELISA was used to determine the levels of inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α). Results Compared with the blank group, the model group showed a significant increase in intracellular orange-red lipid droplets and foam cell formation rate (P<0.05); elevated TC and CE levels (P<0.05); increased M1 macrophage polarization (P<0.05); increased levels of IL-6, IL-1β, and TNF-α (P<0.05); upregulated expression of miR-125a-3p and S1PR3 mRNA (P<0.05); and decreased protein expression of ABCA1 and ABCG1 (P<0.05). Compared with the model group, the curcumin, miR-125a-3p inhibitor, and positive drug groups showed significantly reduced intracellular orange-red lipid droplets and foam cell formation rate (P<0.05); decreased TC, CE, and cholesterol esterification rate (P<0.05); increased M2 macrophage polarization (P<0.05); downregulated expression of miR-125a-3p and S1PR3 mRNA (P<0.05); and increased protein expression of ABCA1 and ABCG1 (P<0.05). Compared with the model group, the curcumin and miR-125a-3p inhibitor groups also exhibited reduced levels of IL-6, IL-1β, and TNF-α (P<0.05). Conclusion Curcumin can effectively inhibit foam cell formation in THP-1-derived macrophages. Its mechanism may be related to downregulation of miR-125a-3p expression, reduction of S1PR3 overexpression, and subsequent upregulation of the cholesterol efflux proteins ABCA1/G1. |
| Key words: curcumin|THP-1-derived macrophage|macrophage|foam cell formation|sphingosine-1-phosphate receptor 3|miR-125a-3p |
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