身痛逐瘀颗粒对类风湿性关节炎大鼠炎症及JAK/STAT信号通路的影响

Effect of Shentong Zhuyu Granules on Inflammation and JAK/STAT Signaling Pathway in Rats with Rheumatoid Arthritis

【目的】观察身痛逐瘀颗粒对类风湿性关节炎(RA)大鼠的治疗作用及机制。【方法】将60只大鼠随机取12只作为正常组,其余48只在模拟“风、寒、湿”的环境下2次免疫构建RA模型。再将全部48只造模成功的大鼠随机分为模型组,身痛逐瘀颗粒高、中、低剂量组,每组12只。对应给药21 d。苏木素-伊红(HE)染色法观察给药后大鼠踝关节滑膜组织病理学并进行评分;比较给药前后大鼠双侧踝关节、双足肿胀度;酶联免疫吸附分析(ELISA)检测给药后大鼠踝关节滑膜组织中炎症因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、干扰素(IFN)-γ含量;Western Blot法检测给药后大鼠踝关节滑膜组织Janus激酶(JAK)/信号转导子和转录激活因子(STAT)通路的蛋白表达。【结果】与正常组比较,模型组大鼠踝关节滑膜增生,软骨细胞结构紊乱,软骨腔中有大量炎细胞浸润,炎细胞浸润程度评分、骨质破坏程度评分显著增加(P<0.05),双侧踝关节、双足肿胀度增加(P<0.05),滑膜组织TNF-α、IL-1β、IL-6、IFN-γ含量,JAK1、STAT3、磷酸化STAT3(p-STAT3)、STAT5、磷酸化STAT 5(p-STAT5)蛋白表达量均显著升高(P<0.05);与模型组比较,身痛逐瘀颗粒高、中、低剂量组上述指标均得到明显改善(P<0.05)。【结论】身痛逐瘀颗粒可有效改善大鼠RA,其作用机制与抑制炎症因子及JAK/STAT信号通路活化有关。

Objective To observe the therapeutic effect and mechanism of Shentong Zhuyu Granules on rheumatoid arthritis(RA)rats.Methods There were 12 rats randomly selected from 60 rats as the normal group,and the remaining 48 rats were gaven two immunization in the simulated environment of‘wind,cold and dampness'to construct the RA model.All 48 successfully modeled rats were randomly divided into model group,Shentong Zhuyu Granules high-,medium-and low-dose groups,with 12 rats in each group.All the groups were given corresponding administration for 21 days.Hematoxylin-eosin(HE)staining was used to observe and score the histopathology of synovial membrane of ankle joint in rats after administration.The swelling degree of bilateral ankle joints and feet of rats was compared before and after administration.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6 and interferon(IFN)-in ankle joint synovial tissue of rats after administration.The protein expressions of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway in synovial tissues of rats were detected by Western Blot.Results Compared with the normal group,the synovial membrane of the rats in the model group proliferated,the structure of chondrocytes was disordered,and a large number of inflammatory cells infiltrated in the cartilage cavity,the scores of inflammatory cell infiltration and bone destruction were significantly increased(P<0.05),the swelling degree of bilateral ankle joints and feet was increased(P<0.05),the contents of TNF-α,IL-1β,IL-6 and IFN-in the synovial tissue,and the protein expression levels of JAK1,STAT3,phosphorylated STAT3(p-STAT3),STAT5 and phosphorylated STAT5(p-STAT5)were significantly increased(P<0.05).Compared with the model group,the above indexes in the high-,medium-and low-dose groups of Shentong Zhuyu Granules were significantly improved(P<0.05).Conclusion Shentong Zhuyu Granules can effectively improve RA in rats,and its mechanism is related to the inhibition of inflammatory factors and the activation of JAK/STAT signaling pathway.