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体外培养的小鼠成纤维细胞(3T3-L1)中银纳米颗粒介导的脂肪生成上调的双重机制。

Dual mechanism of silver nanoparticle-mediated upregulation of adipogenesis in mouse fibroblasts (3T3-L1) in vitro.

机构信息

Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management, St. Sucharskiego 2, 35-225 Rzeszow, Poland.

Department of Chemistry and Food Toxicology, Institute of Food Technology and Nutrition, University of Rzeszow, St. Cwiklinskiej 1A, 35-601 Rzeszow, Poland.

出版信息

Toxicol Appl Pharmacol. 2023 Nov 15;479:116726. doi: 10.1016/j.taap.2023.116726. Epub 2023 Oct 14.

DOI:10.1016/j.taap.2023.116726
PMID:37844778
Abstract

Silver nanoparticles (AgNPs) are widespread in the environment due to the increase in their application e.g. in medicine as part of hard-to-heal wound dressings. Many studies have revealed easy diffusion of AgNPs into deep skin layers through damaged epidermis and contact with e.g. fibroblasts. Therefore, the aim of this study was to evaluate the impact of small-size AgNPs (10 nm) in ppm concentrations on the adipogenesis process in mouse embryo fibroblasts (3T3-L1). The results showed a decrease in the metabolic activity, followed by an increase in the reactive oxygen species (ROS) level in a dose- and time-dependent manner (0-20 ppm). The increased caspase-3 activity was observed only at the highest concentration (20 ppm) of AgNPs. Further analysis showed the ability of the tested NPs to increase the lipid accumulation in adipocytes, similar to ROSI [peroxisome proliferator-activated receptor gamma (PPARγ) agonist], measured by Oil-Red-O staining. Moreover, the analyses evidenced the ability of AgNPs to increase the lipoxygenase activity and malondialdehyde levels, which is probably based on ROS-dependent enhancement of lipid hydroperoxidation. Lastly, a significant increase in the PPARγ, Adiponectin, Resistin, Vegf, and Serpine mRNA expression was shown 6 h after the induction of the differentiation process. Based on the obtained results, it can be concluded that small-size AgNPs increase adipogenesis via ROS- and PPARγ-based mechanisms with potential engagement of crosstalk with the aryl hydrocarbon receptor, which is important due to the widespread application of AgNPs in medicine. However, more studies are needed to elucidate the full mechanism of these NPs in the tested cell model in depth.

摘要

银纳米粒子(AgNPs)由于其应用的增加而广泛存在于环境中,例如作为难以愈合的伤口敷料的一部分应用于医学领域。许多研究表明,AgNPs 很容易通过受损的表皮扩散到深层皮肤层,并与成纤维细胞等接触。因此,本研究旨在评估 ppm 浓度的小尺寸 AgNPs(10nm)对小鼠胚胎成纤维细胞(3T3-L1)脂肪生成过程的影响。结果表明,代谢活性降低,随后活性氧(ROS)水平呈剂量和时间依赖性增加(0-20ppm)。只有在最高浓度(20ppm)的 AgNPs 下才观察到 caspase-3 活性增加。进一步的分析表明,测试的 NPs 具有增加脂肪细胞中脂质积累的能力,类似于 ROSI(过氧化物酶体增殖物激活受体γ(PPARγ)激动剂),通过油红 O 染色测量。此外,分析表明 AgNPs 能够增加脂氧合酶活性和丙二醛水平,这可能基于 ROS 依赖性增强脂质过氧化。最后,在诱导分化过程 6 小时后,显示 PPARγ、脂联素、抵抗素、Vegf 和 Serpine mRNA 表达显著增加。基于获得的结果,可以得出结论,小尺寸 AgNPs 通过 ROS 和 PPARγ 为基础的机制增加脂肪生成,其潜在地参与与芳香烃受体的串扰,这是由于 AgNPs 在医学中的广泛应用而重要。然而,需要更多的研究来深入阐明这些 NPs 在测试细胞模型中的完整机制。

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