文献类型：期刊文献

中文题名：骨痨愈康丸通过JAK/STAT信号通路对类风湿关节炎大鼠滑膜组织的影响

英文题名：Effect of Gulao-Yukang pills on rheumatoid arthritis rat synovial tissue via JAK/STAT signaling pathway

作者：李金益[1];田杰祥[2];宋敏[1,2];王凯[1];李凯[1];胡阳[1];刘路[1]

第一作者：李金益

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730020

第一机构：甘肃中医药大学

年份：2023

卷号：39

期号：8

起止页码：1475

中文期刊名：中国病理生理杂志

外文期刊名：Chinese Journal of Pathophysiology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金资助项目(No.81960832);甘肃中医药大学研究生创新基金资助项目(No.2022CX26);省自然科学基金资助项目(No.22JR11RA131)。

语种：中文

中文关键词：类风湿关节炎;骨痨愈康丸;滑膜;JAK/STAT信号通路

外文关键词：rheumatoid arthritis;Gulao-Yukang pills;synovium;JAK/STAT signaling pathway

摘要：目的:观察骨痨愈康丸(GLYK)对胶原诱导性关节炎(CIA)大鼠滑膜组织的影响,探讨GLYK治疗类风湿关节炎的作用机制。方法:将70只Wistar大鼠,随机分为正常对照(control)组、CIA组、甲氨蝶呤(MTX)组、GLYK组、GLYK+Janus激酶(JAK)受体酪氨酸激酶抑制剂AG490(GLYK+AG490)组和AG490组。除control组外,其余5组建立CIA大鼠模型,每组10只。用药4周后,观察各组大鼠踝关节病理形态;ELISA法检测关节液中白细胞介素6(IL-6)、IL-17、IL-1β、肿瘤坏死因子α(TNF-α)和基质金属蛋白酶3(MMP-3)水平;RT-qPCR与Western blot检测各组大鼠踝关节滑膜组织中JAK2、JAK3、信号转导和转录激活因子3(STAT3)、细胞因子信号抑制因子1(SOCS1)和SOCS3的mRNA及蛋白表达。结果:CIA组大鼠关节液中IL-6、IL-17、IL-1β、TNF-α和MMP-3的水平、滑膜组织中JAK2、JAK3和STAT3蛋白及相关mRNA的表达较control组显著升高(P<0.01),SOCS1和SOCS3蛋白及相关mRNA的表达较control组显著下降(P<0.01);MTX组、GLYK组、GLYK+AG490组和AG490组关节液中IL-6、IL-17、IL-1β、TNF-α和MMP-3的水平、滑膜组织中JAK2、JAK3、STAT3蛋白及相关mRNA的表达较CIA组显著下降(P<0.05),MTX组、GLYK组和AG490组之间相比无显著差异(P>0.05);MTX组、GLYK组、GLYK+AG490组、AG490组SOCS1和SOCS3蛋白及相关mRNA的表达较CIA组显著升高(P<0.05),MTX组、GLYK组和AG490组之间相比无显著差异(P>0.05)。结论:GLYK能有效减轻CIA大鼠炎症反应,其机制可能与抑制JAK/STAT信号通路及调节相关蛋白表达有关。
AIM:This study aims to evaluate the therapeutic effects and regulatory mechanisms of Gulao-Yukang pills(GLYK)on collagen-induced arthritis(CIA)in rat models.METHODS:Seventy Wistar rats were randomly categorized into six groups:normal control,CIA,methotrexate(MTX),GLYK,GLYK supplemented with Janus kinase(JAK)receptor tyrosine kinase inhibitor AG490(GLYK+AG490),and AG490 alone groups.A CIA rat model was established in all groups except control group,each containing 10 rats.After a four-week pharmacological intervention,pathological alterations of the ankle joints were examined in all groups.ELISA was employed to quantify interleukin-6(IL-6),IL-17,IL-1β,tumor necrosis factor-α(TNF-α)and matrix metalloproteinase-3(MMP-3)in the synovial fluid.Moreover,the expression levels of JAK2,JAK3,signal transducer and activator of transcription 3(STAT3),suppressor of cytokine signaling 1(SOCS1)and SOCS3 proteins and their respective mRNA were analyzed using RT-qPCR and Western blot.RESULTS:The rats in CIA group displayed significantly elevated levels of IL-6,IL-17,IL-1β,TNF-αand MMP-3 in synovial fluid(P<0.01),and increased mRNA and protein levels of JAK2,JAK3 and STAT3 in the synovial tissue(P<0.01).Simultaneously,SOCS1 and SOCS3 proteins and related mRNA levels were considerably diminished(P<0.05).Conversely,the rats in MTX,GLYK,GLYK+AG490 and AG490 groups demonstrated a significant reduction in the aforementioned markers compared with CIA group(P<0.05),with no substantial differences observed among MTX,GLYK and AG490 groups(P>0.05).Moreover,the expression of SOCS1 and SOCS3 proteins and related mRNAs markedly increased in MTX,GLYK,GLYK+AG490 and AG490 groups compared with CIA group(P<0.05).CONCLUSION:Gulao-Yukang pills significantly attenuate the inflammatory response in CIA rat model.This beneficial effect appears to be correlated with the inhibition of the JAK/STAT signaling pathway and the regulation of associated protein expression.