Mesh : Rats Humans Animals Arthritis, Experimental / chemically induced drug therapy complications Pyridostigmine Bromide / adverse effects Acetylcholinesterase Dysbiosis / complications Arthritis, Rheumatoid / drug therapy complications Inflammation / drug therapy Terpenes

来  源:   DOI:10.1080/03009742.2023.2196783

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要:
类风湿性关节炎(RA)是一种慢性炎性疾病。吡啶斯的明(PYR),乙酰胆碱酯酶(AChE)抑制剂,在几种与炎症相关的疾病的动物模型中,已被证明可以减少炎症和氧化应激。本研究旨在研究PYR对DarkAgouti(DA)大鼠的前列腺素诱导(PIA)的影响。
DA大鼠皮内灌注普利坦建立PIA模型,用PYR(10mg/kg/天)治疗27天。PYR对滑膜炎症的影响,氧化应激,通过确定关节炎评分来评估肠道微生物群,H&E染色,定量聚合酶链反应,和生化化验,以及16SrDNA测序。
Pristane诱发的关节炎,肿胀的爪子和体重减轻,关节炎评分增加,滑膜增生,骨或软骨侵蚀。PIA组滑膜促炎细胞因子的表达高于对照组。PIA大鼠也显示丙二醛水平升高,一氧化氮,超氧化物歧化酶,血浆中的过氧化氢酶.此外,测序结果表明,多样性,PIA大鼠的肠道菌群组成发生了巨大变化。PYR消除了前列腺素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,与炎症的减轻和肠道菌群失调的纠正有关。这些发现为RA动物模型的药理学干预开辟了新的视角。
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