Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O₂^•−) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of PEG-HCCs on reducing disease severity. PEG-HCCs were internalized by RA-FLS, reduced their intracellular O₂^•−, and reduced multiple measures of their pathogenicity in vitro, including proliferation and invasion. In PIA, PEG-HCCs caused a 65% reduction in disease severity, as measured by a standardized scoring system of paw inflammation and caused a significant reduction in bone and tissue damage, and circulating rheumatoid factor. PEG-HCCs did not induce lymphopenia during PIA. Our study demonstrated a role for O₂^•− and hydroxyl radicals in the pathogenesis of a rat model of RA and showed efficacy of PEG-HCCs in treating a rat model of RA.

中文翻译：

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抗氧化碳纳米颗粒抑制类风湿关节炎大鼠模型中成纤维细胞样滑膜细胞侵袭并减轻疾病严重程度


活性氧参与类风湿性关节炎（RA）的发病机制。我们的目标是确定使用抗氧化剂纳米颗粒（称为聚乙二醇功能化亲水碳簇 (PEG-HCC)）选择性清除超氧化物 (O ₂ ^•− ) 和羟基自由基对成纤维样滑膜细胞致病功能的影响（FLS）来自类风湿性关节炎（RA）患者以及 RA 动物模型的进展。我们使用来自 RA 患者的人类 FLS 来确定 PEG-HCC 内化以及对 FLS 细胞毒性、侵袭性、增殖和蛋白酶产生的影响。我们使用降植烷诱导的关节炎 (PIA) 大鼠模型来评估 PEG-HCC 在降低疾病严重程度方面的益处。 PEG-HCC 被 RA-FLS 内化，减少其细胞内 O ₂ ^•− ，并减少其体外致病性的多种指标，包括增殖和侵袭。在 PIA 中，根据爪子炎症标准化评分系统的测量，PEG-HCC 可使疾病严重程度降低 65%，并显着减少骨和组织损伤以及循环类风湿因子。 PEG-HCC 在 PIA 期间不会诱导淋巴细胞减少。我们的研究证明了O ₂ ^•−和羟基自由基在RA 大鼠模型发病机制中的作用，并显示了PEG-HCC 在治疗RA 大鼠模型中的功效。