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基于STING/NF-κB信号通路探讨蓟黄素对小鼠类风湿性关节炎的影响
黄成硕1, 林娴2, 陈驹3, 郑锦畅1, 梁振1, 郭伟雄1, 陈继铭1
1.广东医科大学附属医院骨科中心, 湛江 524001;2.广东医科大学附属医院超声医学科, 湛江 524001;3.广东医科大学附属医院药学部, 湛江 524001
摘要:
[目的] 评价蓟黄素通过调控STING/NF-κB信号通路对小鼠胶原诱导性关节炎(CIA)的影响。[方法] 取40只SPF级雌性C57BL/6小鼠平均分为空白对照组(Sham)、模型组(CIA)、甲氨蝶呤组(MTX,1 mg/kg)和蓟黄素组(JHS,100 mg/kg),通过胶原免疫法建立小鼠类风湿性关节炎模型。药物干预4周后实验结束,分别检测后爪肿胀度、血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性,观察左侧膝关节形态学变化,测定右侧膝关节STING/NF-κB通路关键蛋白表达水平。[结果] 与CIA组相比,MTX组和JHS组小鼠后爪肿胀度明显降低(P<0.01),血清TNF-α、IL-1β、IL-6、IL-10和MDA水平明显降低,而SOD活性明显增加(P<0.01),膝关节炎症细胞浸润明显减少,软骨组织损伤明显减轻,膝关节STING和p-NF-κB p65/NF-κB蛋白表达水平明显降低(P<0.01)。[结论] 蓟黄素可明显改善类风湿性关节炎,其机制可能通过调控STING/NF-κB信号通路减轻炎症和氧化应激损伤有关。
关键词:  蓟黄素  小鼠  类风湿性关节炎  甲氨蝶呤  STING/NF-κB信号通路
DOI:10.11656/j.issn.1673-9043.2024.11.05
分类号:R285.5
基金项目:广东省中医药局中医药科研项目(20222105);湛江市科技发展专项资金竞争性分配项目(2021A05063)。
The effect of cirsimaritin on rheumatoid arthritis in mice based on STING/NF-κB signaling pathway
HUANG Chengshuo1, LIN Xian2, CHEN Ju3, ZHENG Jinchang1, LIANG Zhen1, GUO Weixiong1, CHEN Jiming1
1.Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;2.Department of Ultrasound Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;3.Department of Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
Abstract:
[Objective] To evaluate the effect of thistle flavescens on collagen-induced arthritis(CIA) in mice by regulating STING/NF-κB signaling pathway. [Methods] Forty SPF grade female C57BL/6 mice were divided into blank control group(Sham), model group(CIA), methotrexate group(MTX, 1 mg/kg) and cirsimaritin group(JHS, 100 mg/kg). The mice rheumatoid arthritis models were established by collagen immunoassay. After 4 weeks of drug intervention, the experiment was completed. Swelling degree of the hind PAWS, levels of TNF-α, IL-1β, IL-6, IL-10, MDA and SOD activity in serum were detected, morphological changes of the left knee joint were observed, and the expression level of STING/NF-κB pathway key proteins in the right knee joint was measured. [Results] Compared with CIA group, the swelling degree of hind PAWS in MTX group and JHS group was significantly decreased(P<0.01), the levels of TNF-α, IL-1β, IL-6, IL-10 and MDA in serum were significantly decreased, while the activity of SOD was significantly increased(P<0.01), the inflammatory cell infiltration of knee joint was significantly decreased, and the cartilage tissue damage was significantly alleviated. The expression levels of STING and P-NF-κB p65/NF-κB protein in knee joint were significantly decreased(P<0.01). [Conclusion] Cirsimaritin can significantly improve rheumatoid arthritis, and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating STING/NF-κB signaling pathway.
Key words:  cirsimaritin  mouse  methotrexate  STING/NF-κB signaling pathway
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