碧萝芷改善骨关节炎进展中细胞环境的机制研究
Study on the mechanism of pycnogenol in improving the cellular microenvironment in osteoarthritis progression
王枫 1李智斌 1孙智平 1李文雄 1肖振1
作者信息
- 1. 陕西中医药大学附属医院创伤二病区(陕西咸阳 712000)
- 折叠
摘要
目的 本研究旨在探究碧萝芷对骨关节炎(OA)大鼠细胞环境的影响,从而为OA的治疗提供一定的理论基础和药物证据.方法 给大鼠注射碘乙酸构建OA模型,用不同剂量的碧萝芷处理OA大鼠.分离OA大鼠的滑膜液、滑膜组织、软骨下骨和成纤维样滑膜细胞.使用酶联免疫吸附法评估OA大鼠膝关节液中的炎症因子的水平,采取流式细胞术、实时荧光定量PCR和蛋白免疫印迹法来检测OA大鼠关节腔滑膜液中免疫细胞的占比和M1/M2型巨噬细胞标志物的水平.通过磁共振成像技术检测OA大鼠软骨下骨的各项指标.结果 碧萝芷以剂量依赖的方式显著抑制OA引起的炎症因子白细胞介素-1β、白细胞介素-6和肿瘤坏死因子α的上调(P＜0.05);碧萝芷抑制OA大鼠膝关节液中活性氧的上调和超氧化物歧化酶的下调(P＜0.05);碧萝芷还可显著诱导OA大鼠关节腔滑膜液M2型巨噬细胞标志物表达量的增加(P＜0.05).在细胞实验中,碧萝芷处理抑制OA大鼠成纤维样滑膜细胞的细胞活力、迁移和侵袭能力(P＜0.05),且促进OA大鼠成纤维样滑膜细胞的细胞凋亡(P＜0.05).此外,碧萝芷以剂量依赖的方式逆转OA引起的大鼠软骨下骨指标改变(P＜0.05),抑制OA引起的大鼠成骨细胞的形成(P＜0.05).结论 碧萝芷可通过促进巨噬细胞M2型极化、抑制成纤维样滑膜细胞功能以及阻碍软骨下骨的成骨发展进而改善OA病理进程.
Abstract
Objective To investigate the effects of Pycnogenol on the cellular microenvironment in osteoarthritis(OA)rats,providing theoretical and pharmacological evidence for OA treatment.Methods An OA rat model was estab-lished via intra-articular injection of iodoacetic acid.OA rats were treated with varying doses of Pycnogenol.Synovial flu-id,synovial tissue,subchondral bone,and fibroblast-like synoviocytes were isolated.Levels of inflammatory cytokines in knee joint fluid were assessed using enzyme-linked immunosorbent assays(ELISA).The proportion of immune cells and the expression of M1/M2 macrophage markers in synovial fluid were measured by flow cytometry,real-time PCR,and Western blotting.Subchondral bone parameters were evaluated using magnetic resonance imaging(MRI).Results Pyc-nogenol significantly suppressed the upregulation of interleukin-1 β,interleukin-6,and tumor necrosis factor-α in OA rats in a dose-dependent manner(P＜0.05).It inhibited the increase in reactive oxygen species and the decrease in su-peroxide dismutase in the knee joint fluid of OA rats(P＜0.05).Pycnogenol also increased the expression of M2 macro-phage markers in the synovial fluid(P＜0.05).In cell experiments,Pycnogenol inhibited fibroblast-like synoviocyte proliferation,migration,and invasion while promoting apoptosis(P＜0.05).Additionally,Pycnogenol reversed changes in subchondral bone metrics in OA rats in a dose-dependent manner(P＜0.05)and inhibited osteoblast formation in-duced by OA(P＜0.05).Conclusion Pycnogenol ameliorates OA progression by promoting M2 macrophage polariza-tion,inhibiting fibroblast-like synoviocyte function,and mitigating subchondral bone remodeling.
关键词
碧萝芷/骨关节炎/炎症因子/巨噬细胞/软骨下骨Key words
pycnogenol/osteoarthritis/inflammatory factors/macrophage/subchondral bone引用本文复制引用
出版年
2025
国家科技期刊平台
NSTL
万方数据