紫花前胡素调节CCL2-CCR2信号轴对类风湿关节炎大鼠免疫功能的影响

doi:10.3969/j.issn.1006-6233.2025.02.010

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摘要 目的: 探讨紫花前胡素(Dec)调节CC趋化因子配体2(CCL2)-CC趋化因子受体2(CCR2)信号轴对类风湿关节炎(RA)大鼠免疫功能的影响。方法: 构建RA大鼠模型,将建模成功的大鼠分为RA组、L-Dec、M-Dec、H-Dec(灌胃40、60、80mg/kg的Dec),Dec+CCL2(灌胃80mg/kg的Dec+腹腔注射5ng CCL2)每组10只,另选择10只大鼠为Control组,Control组和RA组灌胃和注射等量的生理盐水,连续给药4周。测定各组RA大鼠的关节肿胀程度、关节炎指数、机械性痛阈、热刺激缩足反射潜伏期;HE染色观察RA大鼠关节病理学;ELISA检测RA大鼠血清中TNF-α、MMP-3、IL-1β的表达;Western blot检测RA大鼠关节组织中CCL2、CCR2蛋白的表达。结果: Control组关节、骨结构完整清晰;RA组骨结构破坏明显,出现炎性细胞浸润;L-Dec、M-Dec、H-Dec组骨破坏减低,滑膜上皮增生和炎性细胞浸润减少;Dec+CCL2组骨破坏增加,炎性细胞浸润加重。RA组关节肿胀程度、关节炎指数、TNF-α、MMP-3、IL-1β、IgM、IgG、IgA、CCL2、CCR2表达高于Control组,热刺激缩足反射潜伏期、机械性痛阈低于Control组(P<0.05);L-Dec、M-Dec、H-Dec组关节肿胀程度、关节炎指数、TNF-α、MMP-3、IL-1β、IgM、IgG、IgA、CCL2、CCR2表达低于RA组,热刺激缩足反射潜伏期、机械性痛阈高于RA组(P<0.05);Dec+CCL2组关节肿胀程度、关节炎指数、TNF-α、MMP-3、IL-1β、IgM、IgG、IgA、CCL2、CCR2表达高于H-Dec组,热刺激缩足反射潜伏期、机械性痛阈低于H-Dec组(P<0.05)。结论: Dec可以改善RA大鼠的免疫功能,其机制可能是抑制CCL2-CCR2信号轴实现的。

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	王谢
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关键词 ：紫花前胡素, CC趋化因子配体2, CC趋化因子受体2, 类风湿关节炎, 免疫功能

Abstract：Objective: To investigate the effect of decursin (Dec) on the immune function of rheumatoid arthritis (RA) rats by regulating the CC chemokine ligand 2 (CCL2)-CC chemokine receptor 2 (CCR2) signaling axis. Methods: A RA rat model was constructed, and the successfully modeled rats were separated into RA group, L-Dec, M-Dec, H-Dec (gavage of 40, 60, and 80 mg/kg Dec), Dec+CCL2 (gavage of 80 mg/kg Dec+intraperitoneal injection of 5 ng CCL2), with 10 rats in each group. Another 10 rats were selected as the Control group. The Control group and RA group were gavaged and injected with an equal amount of physiological saline for 4 consecutive weeks. The degree of joint swelling, arthritis index, mechanical pain threshold, and paw withdrawal thermal latency (PWTL) of RA rats in each group were measured. The hematoxylin-eosin (HE) staining was applied to observe the joint pathology of RA rats. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the expression of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and interleukin-1 beta (IL-1β) in the serum of RA rats. Western blot was applied to detect the proteins expression of CCL2 and CCR2 in the joint tissues of RA rats. Results: The control group had intact and clear joint and bone structures. The RA group showed obvious bone structure damage with the infiltration of inflammatory cells. The L-Dec, M-Dec, and H-Dec groups showed reduced bone destruction, synovial epithelial proliferation, and inflammatory cell infiltration. The Dec+CCL2 group showed increased bone destruction and aggravated infiltration of inflammatory cells. The degree of joint swelling, arthritis index, the levels of TNF-α, MMP-3, IL-1β, immunoglobulin M (IgM), immunoglobulin G (IgG), immunoglobulin A (IgA), CCL2, and CCR2 in the RA group were significantly higher than those in the Control group, but the PWTL and the mechanical pain threshold were significantly lower (P<0.05). The degree of joint swelling, arthritis index, the levels of TNF-α, MMP-3, IL-1β, IgM, IgG, IgA, CCL2, and CCR2 in the L-Dec, M-Dec, and H-Dec groups were significantly lower than those in the RA group, the PWTL and the mechanical pain threshold were significantly higher (P<0.05). The degree of joint swelling, arthritis index, the levels of TNF-α, MMP-3, IL-1β, IgM, IgG, IgA, CCL2, and CCR2 in the Dec+CCL2 group were significantly higher than those in the H-Dec group, the PWTL and the mechanical pain threshold were significantly lower (P<0.05). Conclusion: Dec can improve the immune function of RA rats, via inhibiting the CCL2-CCR2 signaling axis.

Key words： Decursin CC chemokine ligand 2 CC chemokine receptor 2 Rheumatoid arthritis Immune function

基金资助:湖北省卫生健康委中医药科研立项项目,(编号:ZY2019M053)

通讯作者: 陈丽川

引用本文:

王谢, 王进军, 陈丽川. 紫花前胡素调节CCL2-CCR2信号轴对类风湿关节炎大鼠免疫功能的影响[J]. 河北医学, 2025, 31(2): 234-239.
WANG Xie, WANG Jinjun, CHEN Lichuan. Effect of Decursin on the Immune Function of Rheumatoid Arthritis Rats by Regulating the CCL2-CCR2 Signaling Axis. HeBei Med, 2025, 31(2): 234-239.

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