钩藤碱通过上调SOCS3抑制NOD2/NF-κB信号通路调节巨噬细胞极化影响类风湿性关节炎进展  

Rhynchophylline regulates macrophage polarization by up-regulating SOCS3 to inhibit NOD2/NF-κB signaling pathway,which affects the progression of rheumatoid arthritis

作　　者：陈迎 焦宁 CHEN Ying;JIAO Ning(Department of Pharmacy,The First Affiliated Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院药学部,辽宁沈阳110001

出　　处：《解剖科学进展》2024年第4期345-348,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(2023-MS-01)。

摘　　要：目的探讨钩藤碱介导SOCS3调节巨噬细胞极化对类风湿关节炎大鼠模型的保护作用,并分析其机制。方法Wister大鼠随机分为对照组、模型组、钩藤碱组、钩藤碱+敲减对照组和钩藤碱+敲减SOCS3组。Western blot检测大鼠关节滑膜组织中SOCS3、NOD2和p-NF-κB蛋白表达情况;关节炎指数评分和大体观察大鼠爪子肿胀程度用于评价大鼠关节炎症状;HE染色观察大鼠关节滑膜病理损伤;免疫荧光检测大鼠关节滑膜组织中M1型巨噬细胞标志物CD86和M2型巨噬细胞标志物CD206表达。结果钩藤碱增加CIA大鼠关节滑膜中SOCS3表达,上调大鼠关节炎指数评分,改善大鼠爪子肿胀和关节滑膜病理损伤,降低大鼠关节滑膜中CD86表达并增加CD206表达,下调大鼠关节滑膜中NOD2和p-NF-κB蛋白表达。敲减SOCS3能逆转上述钩藤碱对CIA大鼠的各种作用。结论钩藤碱通过上调SOCS3表达促进巨噬细胞M2极化改善RA诱导的关节损伤,其机制可能与抑制NOD2/NF-κB信号通路激活有关。Objective To explore the protective effect of rhynchophylline-mediated SOCS3 regulating macrophage polarization on rheumatoid arthritis mouse model and analyze its mechanism. Methods Wister rats were randomly divided control group, model group, rhynchophylline group, rhynchophylline+knockdown control group and rhynchophylline+ knockdown SOCS3 group. Western blot was used to detect the expression of SOCS3, NOD2 and p-NF-κB protein in synovial tissue of mouse joints. Arthritis index score and gross observation of paw swelling in rat were used to evaluate arthritis symptoms in rat. HE staining was used to observe the pathological injury of synovium in rat. Immunofluorescence was used to detect the expression of M1 macrophage marker CD86 and M2 macrophage marker CD206 in synovial tissue of mouse joints. Results Rhynchophylline increased the expression of SOCS3 in synovium of CIA rat, up-regulated the arthritis index score of rat, improved paw swelling and pathological injury of synovium of rat, decreased the expression of CD86 and increased the expression of CD206, and down-regulated the expression of NOD2 and p-NF-κB proteins in synovium of rat. Knock-down SOCS3 reversed the up-regulation of rhynchophylline on arthritis index score in rat and improved paw swelling and synovial pathological injury in rat. SOCS3 knockdown could reverse the above effects of rhynchophylline on CIA rats. Conclusion Rhynchophylline could improve RA-induced joint injury by up-regulating the expression of SOCS3, which may be related to inhibiting the activation of NOD2/NF-κB signaling pathway.

关 键 词：钩藤碱 类风湿性关节炎 SOCS3 NOD2/NF-κB信号通路 巨噬细胞极化 

分 类 号：R593.22[医药卫生—内科学]