安徽医科大学学报

目的 探讨白术多糖(PAMK)对类风湿性关节炎(RA)大鼠的抗炎作用及其对Toll样受体4/核因子κB(TLR4/NF-κB)信号通路的影响。方法 采用Ⅱ型胶原诱导建立RA大鼠模型，造模成功后将大鼠分为模型组、阳性药物组(雷公藤多苷片)、PAMK低、高剂量组，同时设置正常对照组，每组12只。给予雷公藤多苷片或PAMK灌胃给药，1次/d,连续4周。测量大鼠体质量、足趾容积和关节炎指数；计算胸腺指数和脾脏指数；HE染色观察踝关节滑膜组织病理学变化；ELISA法检测血清及踝关节滑膜组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)水平；Western blot检测踝关节滑膜组织中总蛋白Toll样受体4(TLR4)、髓样分化因子88(MyD88)、磷酸化核因子κB p65[p-NF-κB p65(Ser536)]及核蛋白NF-κB p65表达水平。结果 与正常对照组比较，模型组大鼠可见滑膜增生、层次不清等病理学改变，体质量降低(P<0.05),足趾容积、关节炎指数以及胸腺、脾脏指数升高(P<0.05),血清及踝关节滑膜组织中IL-1β、IL-6和TNF-α水平以及踝关节滑膜组织中TLR4、MyD88、p-NF-κB p65和NF-κB p65蛋白表达水平升高(P<0.05)。与模型组比较，阳性药物组和PAMK高剂量组大鼠踝关节滑膜组织病理学改变明显改善，体质量升高(P<0.05),足趾容积、关节炎指数以及胸腺、脾脏指数降低(P<0.05),血清及踝关节滑膜组织中IL-1β、IL-6和TNF-α水平以及踝关节滑膜组织中TLR4、MyD88、p-NF-κB p65和NF-κB p65蛋白表达水平降低(P<0.05),而PAMK低剂量组大鼠以上各指标与模型组比较差异均无统计学意义(P>0.05)。结论 PAMK可减轻机体炎症反应，改善RA,其机制可能与抑制TLR4/NF-κB信号通路的活化有关。

Objective To investigate the anti-inflammatory effect of polysaccharide from atractylodes atractylodes(PAMK) on rheumatoid arthritis(RA) rats and its effect on Toll like receptor 4/nuclear factor kappa-B(TLR4/NF-κB) signaling pathway. Methods RA rat model was induced by type Ⅱ collagen, after successful modeling, the rats were divided into model group, positive drug group(Tripterygium wilfordii polyglycoside tablet), PAMK low-dose and high-dose groups, normal control group was also set, with 12 rats in each group. Tripterygium wilfordii polyglycoside tablets or Atractylodes macrocephala polysaccharide were administered intragastric administration, once a day for 4 weeks. The body weight, paw swelling rate and arthritis index of rats were measured; the thymus index and spleen index were calculated; HE staining was used to observe the histopathological changes of synovial membrane of ankle joint; The levels of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in serum and synovial tissue of ankle were determined by ELISA; The expression levels of total protein TLR4, MyD88, phosphorylated NF-κB p65(Ser536) and nuclear protein NF-κB p65 in synovial tissue of ankle were detected by Western blot. Results Compared with the normal control group, synovial hyperplasia and unclear layers were observed in the model group, body weight decreased(P<0.05), paw swelling rate, arthritis index, thymus index and spleen index increased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in serum and synovial tissue of ankle, and the protein expressions of TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in synovial tissue of ankle increased(P<0.05). Compared with model group, the histomathological changes of synovial of ankle joint in positive drug group and PAMK high-dose group were significantly improved, body weight increased(P<0.05), paw swelling rate, arthritis index, thymus index and spleen index decreased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in serum and synovial tissue of ankle, and the protein expressions of TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in synovial tissue of ankle decreased(P<0.05), however, there were no significant differences in the above indexes between PAMK low-dose group and model group(P>0.05). Conclusion PAMK can reduce the inflammatory response and improve RA, and the mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway activation.