首页|十七烷基间苯二酚对氧化三甲胺诱导的人脐静脉内皮细胞损伤的作用机制

十七烷基间苯二酚对氧化三甲胺诱导的人脐静脉内皮细胞损伤的作用机制

Mechanism of Trimethylaminc-N-Oxide-Induced Human Umbilical Vein Endothelial Cell Damage by 5-Heptadecylresorcinol

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为探究全麦食品中生物活性物质十七烷基间苯二酚(5-heptadecylresorcinol,AR-C17)对动脉粥样硬化的作用机制,采用氧化三甲胺(trimethylamine-N-oxide,TMAO)诱导人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC),建立损伤模型,通过检测内皮细胞迁移、线粒体功能、凋亡水平及其相关蛋白表达,揭示AR-C17对HUVEC的保护效果及其作用机制.研究结果表明:不同浓度的AR-C17(0.5、1.0、2.0 μmol/L)能够显著抑制TMAO诱导的细胞存活率下降,HUVEC存活率分别提升至69%、71%和72%;3种剂量的AR-C17均能显著改善HUVEC内皮功能,细胞迁移率分别提升至47%、55%和71%.线粒体功能评价结果显示,AR-C17能够显著降低TMAO诱导的HUVEC胞内及线粒体活性氧水平,缓解线粒体膜电位紊乱,同时提高细胞的基础呼吸强度、ATP生成量和最大呼吸氧气消耗速率,表明AR-C17显著缓解了 TMAO诱导的线粒体功能紊乱.细胞凋亡结果显示,高剂量的AR-C17能够使TMAO诱导的HUVEC凋亡率由32%降低至19%.线粒体依赖凋亡途径相关蛋白表达水平结果表明,AR-C17能够显著降低B细胞淋巴瘤因子-2(B-cell lymphoma-2,BCL-2)相关X蛋白和BCL-2表达量的比值,同时抑制细胞色素C在细胞质中的表达并且提高其在线粒体中的表达水平.研究结果表明,AR-C17可通过改善HUVEC线粒体功能并抑制线粒体依赖性凋亡,进而缓解TMAO诱导的HUVEC损伤.研究旨在为具有预防心血管疾病的全谷物功能食品的开发与利用提供理论基础.
To investigate the anti-atherosclerosis effect and mechanism of 5-heptadecylresorcinol(AR-C17),a bioactive substance in whole grain foods,human umbilical vein endothelial cells(HUVEC)were induced with trimethylamine-N-oxide(TMAO)to establish adamage model.The protective effect of AR-C17 on HUVEC and its mechanism were investigated by detecting endothlial cell migration,mitochondrial function,apoptosis level and related protein expression.The results showed that 0.5,1.0 and 2.0 μmol/L AR-C17 could significantly inhibit TMAO-induced cell death,and the cell viability of HUVEC were increased to 69%,71%and 72%,respectively.Three dosages of AR-C17 also significantly improved the endothelial function of HUVEC,and the cell migration rates were increased to 47%,55%and 71%.The result of mitochondrial function showed that AR-C17 could significantly reduce the level of intracellular and mitochondrial reactive oxygen species induced by TMAO and the disorder of mitochondrial membrane potential.AR-C17 significantly increased the basal respiration,ATP production and maximum respiratory oxygen consumption rates,indicating that AR-C1 7 significantly alleviated the TMAO-induced mitochondrial dysfunction.Meanwhile,the results showed that AR-C17 reduced the TMAO-induced apoptosis rate of HUVEC from 32%to 19%.The expression levels of proteins related to the mitochondria-dependent apoptotic pathway indicated that AR-C17 significantly reduced the ratio of B-cell lymphoma-2(BCL-2)-associated X protein and BCL-2 expression,while inhibiting cytochrome C expression in the cytoplasm and increasing its expression level in mitochondria.The results showed that AR-C17 alleviated TMAO-induced HUVEC injury by improving mitochondrial function and inhibiting mitochondria-dependent apoptosis.The aim of this study was to provide the theoretical basis for development and utilization of whole grain functional foods against cardiovascular.

5-heptadecylresorcinolendothelial celltrimethylamine-N-oxideapoptosismitochondrial function

杨子慧、张眙曼、王子元、叶高琪、刘洁、王静

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北京工商大学老年营养与健康教育部重点实验室,北京 100048

十七烷基间苯二酚 内皮细胞 氧化三甲胺 凋亡 线粒体功能

2025

食品科学技术学报
北京工商大学

食品科学技术学报

北大核心
影响因子:1.967
ISSN:2095-6002
年,卷(期):2025.43(1)