目前治疗类风湿性关节炎（RA）的药物中，副作用较少的药物并不多。灵芝多糖肽（GLPP）具有良好的免疫调节作用，但其在治疗RA方面的有效性尚不清楚。本研究旨在研究GLPP在胶原诱导性关节炎（CIA）大鼠中的抗类风湿性活性及可能的机制。雄性Wistar大鼠经尾根皮下注射牛Ⅱ型胶原制备CIA模型，并口服100或200mg/kg的GLPP，持续35天。对大鼠进行了掌厚度测量、关节炎临床评分、步态分析、器官指数测定、血细胞计数、微CT成像和病理染色。使用商业试剂盒测定肝肾功能，使用ELISA试剂盒测定抗体水平。通过Western blotting测定了与RA相关的蛋白水平。GLPP有效缓解了CIA症状，降低了免疫器官指数、抗体水平和全身器官损伤。GLPP降低了CIA大鼠关节组织中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6、基质金属蛋白酶（MMP）2、MMP9、MMP13、BCL-2、OPN、β-连环蛋白和缺氧诱导因子（HIF）-1α蛋白表达，增加了BAX蛋白表达。此外，GLPP降低了p65、IκB-α和ERK1/2的磷酸化水平。GLPP通过抑制NF-κB和MAPK途径的活化有效缓解了CIA大鼠的RA症状。本研究表明，源于蘑菇的多糖肽对RA具有有希望的治疗效果。版权所有©2023 Elsevier GmbH出版。

Not many drugs with fewer side effects are available for the treatment of rheumatoid arthritis (RA). Ganoderma lucidum polysaccharide peptide (GLPP) has good immunomodulatory effects, but whether it is effective in managing RA is not clear.This study was conducted to examine the anti-RA activity and possible mechanisms of GLPP in collagen-induced arthritis (CIA) rats.Male Wistar rats were intradermally injected with bovine type II collagen in the tail base to establish the CIA model and were orally administered 100 or 200 mg/kg GLPP for 35 days. Paw thickness, clinical arthritis scores, gait analysis, organ index determination, blood cell counts, micro-CT imaging and pathological staining were performed on the rats. Liver and kidney function were measured by commercial kits, and antibody levels were measured by ELISA kits. RA-related protein levels were detected by Western blotting.GLPP effectively alleviated CIA symptoms and reduced immune organ indexes, antibody levels and systemic organ injury. GLPP decreased the protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)2, MMP9, MMP13, BCL-2, OPN, β-Catenin, and hypoxia inducible factor (HIF)-1α and increased the protein expression of BAX in the joint tissues of CIA rats. Moreover, GLPP decreased the phosphorylation levels of p65, IκB-α and ERK1/2.GLPP effectively alleviated RA symptoms in CIA rats by inhibiting the NF-κB and MAPK pathways. This study suggests a promising therapeutic effect of mushroom-derived polysaccharide peptides on RA.Copyright © 2023. Published by Elsevier GmbH.