Zeng M, Issotina Zibrila A, Li X, Liu X, Wang X, Zeng Z, Wang Z, He Y, Meng L, Liu J
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an, PR China.
National Joint Engineering Research Center of Biodiagnostics and Biotherapy, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, PR China.
Scand J Rheumatol. 2023 Nov;52(6):627-636. doi: 10.1080/03009742.2023.2196783. Epub 2023 Jun 20.
Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats.
DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing.
Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis.
The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.
类风湿性关节炎（RA）是一种慢性炎症性疾病。吡啶斯的明（PYR）是一种乙酰胆碱酯酶（AChE）抑制剂，已证实在几种与炎症相关疾病的动物模型中可减轻炎症和氧化应激。本研究旨在探讨PYR对暗褐鼠（DA）中 pristane 诱导的关节炎（PIA）的影响。
给 DA 大鼠皮内注射 pristane 以建立 PIA 模型，用 PYR（10 mg/kg/天）治疗 27 天。通过测定关节炎评分、苏木精-伊红染色、定量聚合酶链反应、生化分析以及 16S rDNA 测序来评估 PYR 对滑膜炎症、氧化应激和肠道微生物群的影响。
Pristane 诱发了关节炎，出现爪肿胀和体重减轻，关节炎评分增加、滑膜增生以及骨或软骨侵蚀。PIA 组滑膜中促炎细胞因子的表达高于对照组。PIA 大鼠血浆中丙二醛、一氧化氮、超氧化物歧化酶和过氧化氢酶水平也升高。此外，测序结果表明 PIA 大鼠肠道微生物群的丰富度、多样性和组成发生了显著变化。PYR 消除了 pristane 诱导的炎症和氧化应激，并纠正了肠道微生物群失调。
本研究结果支持 PYR 在 DA 大鼠 PIA 中的保护作用，这与炎症减轻和肠道微生物群失调的纠正有关。这些发现为 RA 动物模型的药物干预开辟了新的前景。
