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类叶牡丹关节注射液治疗类风湿性关节炎的作用机制
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| 篇名： | 类叶牡丹关节注射液治疗类风湿性关节炎的作用机制 |
| TITLE： | Mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis |
| 摘要： | 目的 探究类叶牡丹关节注射液治疗类风湿性关节炎（RA）的作用机制。方法类叶牡丹中的主要皂苷类成分通过SwissTargetPrediction网站获取作用靶点，与从GeneCards、OMIM数据库中收集的RA治疗靶点并取交集，基于网络药理学建立交互网络，进行基因本体功能、京都基因与基因组百科全书（KEGG）通路富集分析。采用大耳兔背部注射弗氏完全佐剂建立RA模型进行验证，比较各组大耳兔关节炎指数评分、膝关节直径和痛阈值变化，观察滑膜组织形态变化，检测血清和关节滑液中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、IL-6水平以及滑膝关节膜组织中Janus激酶2（JAK2）、信号转导与转录激活因子3（STAT3）蛋白的磷酸化水平。结果网络药理学筛选出类叶牡丹关节注射液与RA的交集靶点有143个，构建“药物-成分-靶点”网络后获取核心成分为刺囊酸、齐墩果酸、常春藤皂苷元、葳岩仙皂苷A、葳岩仙皂苷C等；蛋白质-蛋白质相互作用网络构建排前10名的核心靶点分别为SRC、STAT3、MAPK1、EGFR、PIK3CA、MAPK3、GRB2、JUN、PTPN11、JAK2；KEGG通路富集分析结果显示，类叶牡丹关节注射液治疗RA主要涉及JAK/STAT信号通路等。实验验证结果显示，与模型组比较，类叶牡丹关节注射液可减轻大耳兔膝关节肿胀和滑膜层增生，使下层结缔组织增生减少、炎症细胞和毛细血管数量减少；显著降低关节炎指数评分（类叶牡丹低剂量组除外），膝关节直径，血清和关节滑液中TNF-α、IL-1β、IL-6水平以及JAK2、STAT3蛋白的磷酸化水平（P＜0.05或P＜0.01）；显著升高痛阈值水平（P＜0.01）。结论类叶牡丹关节注射液中刺囊酸、齐墩果酸、常春藤皂苷元、葳岩仙皂苷A、葳岩仙皂苷C可能是缓解RA炎症反应的核心成分，其作用机制可能与抑制JAK/STAT信号通路、减轻炎症反应有关。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis （RA）. METHODS The targets of main saponins in C. robustum Maxim were obtained from Swiss Target Prediction， and the RA treatment targets collected from the GeneCards and OMIM database were intercrossed to establish an interaction network based on network pharmacology. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were performed. RA model was established by injecting complete Freund’s adjuvant into the back of rabbits for verification. The arthritis index score， knee diameter and pain threshold of rabbits were compared. Pathological examination of rabbit synovial tissue was carried out. The levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL-1β） and IL-6 in rabbit serum and synovial fluid were detected. The phosphorylation levels of tyrosine protein Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） proteins in rabbit synovium were detected. RESULTS Network pharmacology identified 143 intersection targets between the drug and RA. After the construction of the “drug-component-target” network， the core components of the network were echinocystic acid， oleanolic acid， hederagenin， cauloside A and cauloside C， etc. Additionally， the top 10 core targets of PPI network were SRC， STAT3， MAPK1， EGFR， PIK3CA， MAPK3， GRB2， JUN， PTPN11 and JAK2. The results of KEGG pathway analysis showed that the JAK/STAT signaling pathway was mainly involved in the treatment of RA by joint injection of C. robustum Maxim. Results of validation test showed that compared with model group， joint injection of C. robustum Maxim could reduce the swelling of rabbit knee joint， relieve the hyperplasia of synovial layer， reduce the hyperplasia of lower connective tissue， and reduce the number of inflammatory cells and capillaries. The arthritis index score （excluding low-dose group of C. robustum Maxim）， knee diameter， the levels of TNF-α， IL-1β and IL-6 in serum and synovial fluid， and the protein phosphorylation levels of JAK2 and STAT3 were decreased significantly （P＜0.05 of P＜0.01）， while the pain threshold were reduced significantly （P＜0.01）. CONCLUSIONS The core components that may alleviate the inflammatory response of RA in joint injection of C. robustum Maxim could include echinocystic acid， oleanolic acid， hederagenin， cauloside A， and cauloside C. Its mechanism may be related to the inhibition of JAK/STAT signaling pathway and the reduction of inflammatory responses. |
| 期刊： | 2025年第36卷第08期 |
| 作者： | 吕邵娃；邬芸煜；刘泉莉；任雨涵；郭玉岩；匡海学 |
| AUTHORS： | LYU Shaowa，WU Yunyu，LIU Quanli，REN Yuhan，GUO Yuyan，KUANG Haixue |
| 关键字： | 类叶牡丹；类叶牡丹关节注射液；类风湿性关节炎；JAK/STAT信号通路；网络药理学 |
| KEYWORDS： | Caulophyllum robustum Maxim； Joint injection of Caulophyllum robustum Maxim； rheumatoid arthritis； JAK/ |
| 阅读数： | 2 次 |
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