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不同剂量灵芝酸A对多关节炎小鼠类风湿性关节炎模型伤害性感受行为和炎症参数的影响

Effects of different doses of Ganoderic Acid A on nociceptive behaviour and inflammatory parameters in polyarthritic mice rheumatoid arthritis model.

作者信息

Guzel Erdogan Derya, Demır Ayşenur, Baylan Hüseyin, Budak Özcan, Cokluk Erdem, Tanyerı Pelin

机构信息

Department of Physiology Faculty of Medicine, Sakarya University, Sakarya, Turkey.

Department of Physiology, Institute of Health Sciences, Sakarya University, Sakarya, Turkey.

出版信息

Sci Rep. 2025 May 6;15(1):15759. doi: 10.1038/s41598-025-99917-6.

DOI:10.1038/s41598-025-99917-6
PMID:40328991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056153/
Abstract

The frequency of autoimmune diseases such as rheumatoid arthritis is increasing annually. Current treatments for these diseases cause new problems due to their side effects. In this study, we investigated the impact of Ganoderic Acid A (GAA), a potent anti-inflammatory herbal molecule, to evaluate the potential efficacy of GAA in alleviating Rheumatoid arthritis (RA)-associated clinical and histopathological manifestations. 40 Balb/c male mice were randomly divided into five groups (n = mice number per each group) as control (C), acetic acid (AA), rheumatoid arthritis (RA), low dose GAA (LGA) and high dose GAA (HGA) groups. Collagen emulsion was applied intra-articularly (ia), and complete Freund's adjuvant (CFA) was applied subcutaneously (sc) to the RA and GA groups to induce an experimental model of rheumatoid arthritis. Other groups were given physiologic saline (PS) or AA at the same dose and in the same way. The procedures were repeated on the 22nd day; however, incomplete Freund's adjuvant was applied to the RA and GA groups instead of CFA. PS was given to groups C, AA and RA for 9 days starting from the 22nd day; GAA was applied to the LGA (20 mg/kg) and HGA (40 mg/kg) groups by gavage. We evaluated body weight, arthritis score, knee temperature, knee circumference, behavioural assessment of pain, gait, tail-flick test, hot plate test, locomotor activity test, lower extremity index, spectrophotometric and histopathological evaluation methods, respectively. Compared to the RA group, the clinical arthritis score was reduced in the HGA group (p < 0.05). GAA significantly reduced knee temperatures and knee circumference, with changes in hot plate scores and tail flip test response. In the GAA groups, serum concentrations of AST, IL-6, TNF-α, NFkB were reduced, and joint damage and arthritis scores were also reduced histologically (p < 0.05). The results of this study suggest that the arthritis regressed with GAA treatment. Edema and inflammation were found to be reduced in the GAA groups compared with the RA group. GAA treatment resulted in significant improvements in behavioural activity, reduced inflammation and the damage to cartilage and bone structure and had an antinociceptive effect.

摘要

类风湿关节炎等自身免疫性疾病的发病率逐年上升。目前针对这些疾病的治疗方法因其副作用引发了新的问题。在本研究中,我们研究了强效抗炎草药分子灵芝酸A(GAA)的影响,以评估GAA缓解类风湿关节炎(RA)相关临床和组织病理学表现的潜在疗效。将40只雄性Balb/c小鼠随机分为五组(n =每组小鼠数量),即对照组(C)、醋酸组(AA)、类风湿关节炎组(RA)、低剂量GAA组(LGA)和高剂量GAA组(HGA)。向RA组和GA组关节内注射(ia)胶原蛋白乳剂,并皮下注射(sc)完全弗氏佐剂(CFA)以诱导类风湿关节炎实验模型。其他组以相同剂量和方式给予生理盐水(PS)或AA。在第22天重复上述操作;然而,RA组和GA组改为注射不完全弗氏佐剂而非CFA。从第22天开始,C组、AA组和RA组给予PS,持续9天;LGA组(20 mg/kg)和HGA组(40 mg/kg)通过灌胃给予GAA。我们分别评估了体重、关节炎评分、膝关节温度、膝关节周长、疼痛行为评估、步态、甩尾试验、热板试验、运动活动试验、下肢指数、分光光度法和组织病理学评估方法。与RA组相比,HGA组的临床关节炎评分降低(p < 0.05)。GAA显著降低了膝关节温度和膝关节周长,同时热板评分和甩尾试验反应也有变化。在GAA组中,血清AST、IL-6、TNF-α、NFkB浓度降低,组织学上关节损伤和关节炎评分也降低(p < 0.05)。本研究结果表明,GAA治疗可使关节炎病情缓解。与RA组相比,GAA组的水肿和炎症减轻。GAA治疗使行为活动显著改善,炎症减轻,软骨和骨结构损伤减少,并具有抗伤害感受作用。

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