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

作　　者：王枫 李智斌 孙智平 李文雄 肖振 WANG Feng;LI Zhi-bin;SUN Zhi-ping;LI Wen-xiong;XIAO Zhen(Trauma Ward 2,the Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China)

机构地区：[1]陕西中医药大学附属医院创伤二病区,陕西咸阳712000

出　　处：《广东医学》2025年第1期33-40,共8页Guangdong Medical Journal

基　　金：陕西省自然科学基础研究计划一般项目(青年)(2023-JC-QN-0978);陕西省中医药管理局-秦创原中医药创新研发转化项目(2022-QCYZH-029)。

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。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 established via intra-articular injection of iodoacetic acid.OA rats were treated with varying doses of Pycnogenol.Synovial fluid,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 Pycnogenol significantly suppressed the upregulation of interleukin-1β,interleukin-6,and tumor necrosis factor-αin OA rats in a dose-dependent manner(P<0.05).It inhibited the increase in reactive oxygen species and the decrease in superoxide dismutase in the knee joint fluid of OA rats(P<0.05).Pycnogenol also increased the expression of M2 macrophage 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 induced by OA(P<0.05).Conclusion Pycnogenol ameliorates OA progression by promoting M2 macrophage polarization,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 

分 类 号：R684.3[医药卫生—骨科学] R285.5[医药卫生—外科学]