透明质酸(hyaluronic acid, HA)凭借其良好的生物活性与成熟的发酵工艺,已成为食品、化妆品及医药等多个领域中广泛应用的原料之一。尽管HA被证实对皮肤健康具有显著的促进作用,但其通过细胞间相互作用抵御皮肤缺氧损伤的作用机制尚不明确。该研究采用4种不同分子质量HA预处理成纤维细胞制备条件培养基(HA-conditioned medium, HA-CM),并进一步评估HA-CM对角质形成细胞缺氧损伤的改善作用。结果表明,低分子质量HA2(30.8 kDa)在促进成纤维细胞分泌转化生长因子-β1(transforming growth factor-beta 1, TGF-β1)与血管内皮生长因子(vascular endothelial growth factor, VEGF),以及抑制白细胞介素-1α(interleukin-1 alpha, IL-1α)释放方面,显示出最强的效应。此外,HA2-CM对缺氧损伤HaCaT细胞的保护作用最为显著,表现为活性氧(reactive oxygen species, ROS)水平降低,肿瘤坏死因子-α(tumor necrosis factor-alpha, TNF-α)和白细胞介素-6(interleukin-6, IL-6)分泌减少以及细胞凋亡率下降。上述结果表明HA通过重塑成纤维细胞的分泌表型,以TGF-β1/VEGF为关键旁分泌媒介,协同激活核因子E2相关因子2(nuclear factor erythroid 2-related factor 2, Nrf2)/血红素加氧酶-1(heme oxygenase-1, HO-1)通路的抗氧化作用,从而阐释了其对皮肤缺氧损伤进行多靶点调控的机制。该文为综合利用透明质酸开发高附加值的食品指明了方向,也为基于分子质量精准设计的抗缺氧干预策略提供了重要参考。
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