Rapid development of gold nanoparticles (GNPs) in delivering pharmaceutics and therapeutics approaches still linger the concerns of their toxic effects. Nonalcoholic steatohepatitis (NASH) is characterized by excessive lipid accumulation and overt hepatic inflammatory damage, and is the leading cause of chronic liver disease worldwide. This study aimed to assess the potential hepatic effects of GNPs on NASH phenotype and progression in mice. Mice were fed a MCD diet for 8 weeks to elicit NASH and then intravenously injected with PEG-GNPs at a single dose of 1, 5, and 25 mg/kg-bw. After 24 h and 1 week of administration, the levels of plasma ALT and AST, and the number of lipid droplets, the degree of lobular inflammation and the contents of triglycerides and cholesterols in the livers of the NASH mice significantly increased compared with the untreated NASH mice, indicating that the severity of MCD diet-induced NASH-like symptoms in mice increased after PEG-GNP administration. Moreover, the aggravated hepatic steatosis in a manner involving altered expression of the genes related to hepatic de novo lipogenesis, lipolysis, and fatty acid oxidation was observed after PEG-GNP administration. Additionally, the RNA levels of biomarkers of hepatic pro-inflammatory responses, endoplasmic reticulum stress, apoptosis, and autophagy in MCD-fed mice increased compared with the untreated NASH group. Moreover, PEG-GNP-treated NASH mice displayed an increase in MCD diet-induced hepatic fibrosis, revealed by massive deposition of collagen fiber in the liver and increased expression of fibrogenic genes. Collectively, these results suggest that hepatic GNP deposition after PEG-GNP administration increase the severity of MCD-induced NASH phenotype in mice, which is attributable to, in large part, increased steatohepatitic injury and liver fibrosis in mice.

金纳米颗粒（GNP）在药物和治疗方法方面的快速发展仍然令人担忧其毒性作用。非酒精性脂肪性肝炎（NASH）的特点是脂质过度积累和明显的肝脏炎症损伤，是全球慢性肝病的主要原因。本研究旨在评估 GNP 对小鼠 NASH 表型和进展的潜在肝脏影响。给小鼠喂食 MCD 饮食 8 周以诱发 NASH，然后以 1、5 和 25 mg/kg-bw 的单剂量静脉注射 PEG-GNP。给药24 h和1周后，NASH小鼠的血浆ALT和AST水平以及脂滴数量、小叶炎症程度以及肝脏中甘油三酯和胆固醇的含量与未治疗的NASH相比显着升高小鼠，表明在给予 PEG-GNP 后，MCD 饮食诱导的小鼠 NASH 样症状的严重程度增加。此外，在施用PEG-GNP后，观察到肝脏脂肪变性加重，其方式涉及与肝脏从头脂肪生成、脂肪分解和脂肪酸氧化相关的基因的表达改变。此外，与未治疗的 NASH 组相比，MCD 喂养的小鼠中肝脏促炎症反应、内质网应激、细胞凋亡和自噬的生物标志物的 RNA 水平有所增加。此外，PEG-GNP 治疗的 NASH 小鼠表现出 MCD 饮食诱导的肝纤维化增加，这通过肝脏中胶原纤维的大量沉积和纤维形成基因的表达增加来揭示。总的来说，这些结果表明，给予 PEG-GNP 后，肝脏 GNP 沉积会增加小鼠中 MCD 诱导的 NASH 表型的严重程度，这在很大程度上可归因于小鼠脂肪肝损伤和肝纤维化的增加。