The purpose of this article was to explore the effects of gold nanoparticles (GNPs) and silver nanoparticles (SNPs) with different cytotoxicities on human dermal fibroblasts (HDFs) at the metabolic level. First, ∼20 nm of GNPs and SNPs were prepared, and their effects on the proliferation of HDFs were evaluated. Then, a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4, 8 and 24 h of treatment. Furthermore, the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments. The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h, while the cytotoxicity of the SNPs reached grade 1 after 72 h. By using metabolomics analysis, 29, 30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment, while SNPs induced the differential expression of 13, 33 and 22 metabolites after 4, 8 and 24 h of treatment, respectively. Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis, respectively. The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway (the key metabolite of which was glutathione) and the citrate cycle pathway (the key metabolite of which was malic acid). Based on the experiments used to verify the key metabolites and key metabolic pathways, it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity. After exposure to SNPs, the citric acid content was increased, mainly through the citrate cycle pathway, thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.

中文翻译：

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金和银纳米粒子对人类皮肤成纤维细胞代谢影响的比较研究。

本文的目的是在代谢水平上探索具有不同细胞毒性的金纳米颗粒（GNP）和银纳米颗粒（SNP）对人皮肤成纤维细胞（HDF）的影响。首先，制备约20 nm的GNP和SNP，并评估它们对HDF增殖的影响。然后，使用代谢组学技术分析处理4、8和24小时后GNP和SNP对HDF中代谢物表达谱的影响。此外，通过差异表达代谢物的表达模式分析和代谢途径分析，确定了GNP和SNP与HDF相互作用的关键代谢物和关键代谢途径，最后通过实验验证。细胞毒性实验结果表明，GNPs处理72 h后无细胞毒性，而72 h后SNPs的细胞毒性达到1级。通过代谢组学分析，显示GNP处理后HDF中29、30和27种代谢物差异表达，而SNP在处理4、8和24小时后分别诱导13、33和22种代谢物差异表达。通过表达模式分析和代谢途径分析分别确定了GNP和SNP组中的6个和4个候选关键代谢物。GNP和SNP组中的关键代谢途径被鉴定为谷胱甘肽代谢途径（其关键代谢产物为谷胱甘肽）和柠檬酸盐循环途径（其关键代谢产物为苹果酸）。根据用于验证关键代谢物和关键代谢途径的实验，发现GNP处理后谷胱甘肽的增加可能会触发氧化应激保护机制，从而避免细胞毒性。暴露于SNPs后，柠檬酸含量增加，主要通过柠檬酸循环途径，从而抑制了苹果酸的合成，从而影响ATP的形成并最终导致细胞毒性。