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通过Wnt/β-catenin信号通路探究莪术二酮对小鼠骨关节炎的作用
黄成硕1, 陈驹2, 林颢3, 梁振3, 郑锦畅3, 郭伟雄3, 曾莉1
1.澳门科技大学中医药学院, 澳门 999078;2.广东医科大学附属医院药学部, 湛江 524001;3.广东医科大学附属医院骨科中心, 湛江 524001
摘要:
目的 探讨莪术二酮通过调控Wnt/β-catenin信号通路对小鼠骨关节炎的影响。方法 30只SPF级雄性C57BL/6小鼠随机分为假手术组(Sham组)、模型组(OA组)和莪术二酮组(ESET组,60 mg/kg),每组10只,采用内侧半月板失稳术构建骨关节炎模型,连续灌胃给药4周。番红O和苏木精-伊红(HE)染色法观察膝关节形态学变化,酶联免疫吸附实验(ELISA)法检测血清中炎症因子[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)]和化学发光法检测氧化应激指标[谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)],免疫组化和蛋白免疫印迹(Western Blot)法检测膝关节Wnt/β-catenin通路关键蛋白的表达水平。结果 与Sham组比较,OA组小鼠膝关节大量炎症细胞浸润,软骨组织损伤严重,血清TNF-α、IL-1β、IL-6、IL-10和MDA水平明显升高(P<0.01),而SOD和GSH-Px活性降低(P<0.01),膝关节wnt3a和β-catenin蛋白相对表达水平升高(P<0.01)。莪术二酮干预后可明显改善上述指标。结论 莪术二酮可能通过调控Wnt/β-catenin信号通路减轻炎症和氧化应激损伤,从而改善骨关节炎。
关键词:  莪术二酮  骨关节炎  小鼠  Wnt/β-catenin信号通路
DOI:10.11656/j.issn.1673-9043.2025.09.05
分类号:R285.5
基金项目:广东省医学科学技术研究基金项目(B2024110,B2024006)。
The effects of curdione on osteoarthritis in mice based on Wnt/β-catenin signaling pathway
HUANG Chenshuo1, CHEN Ju2, LIN Hao3, LIANG Zhen3, ZHENG Jinchang3, GUO Weixiong3, ZENG Li1
1.School of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China;2.Department of Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;3.Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
Abstract:
Objective To investigate the effects of curdione on osteoarthritis in mice by regulating Wnt/β-catenin signaling pathway. Methods Thirty SPF grade male C57BL/6 mice were randomly divided into Sham operation group(Sham), model group(OA) and curdione group(ESET, 60 mg/kg), with 10 mice in each group. The osteoarthritis model was constructed by medial meniscus instability. The drug was given by continuous gavage for 4 weeks. The morphological changes of knee joint were observed by saffrine O and HE staining, and serum inflammatory factors(TNF-α, IL-1β, IL-6, IL-10) were detected by ELISA and oxidative stress indexes(GSH-PX, SOD, MDA) were detected by chemiluminescence. The expression levels of key proteins in Wnt/β-catenin pathway were detected by immunohistochemistry and Western Blot. Results Compared with Sham group, a large number of inflammatory cells infiltrated the knee joint of mice in OA group, cartilage tissue was seriously damaged, serum levels of TNF-α, IL-1β, IL-6, IL-10 and MDA were significantly increased(P < 0.01), while the activities of SOD and GSH-PX were significantly decreased(P < 0.01). The relative expression levels of wnt3a and β-catenin in knee joint were significantly increased(P < 0.01). The above indexes can be improved obviously after curdione intervention. Conclusion Curdione may ameliorate osteoarthritis by regulating the Wnt/β-catenin signaling pathway to reduce inflammation and oxidative stress damage.
Key words:  curdione  osteoarthritis  mice  Wnt/β-catenin signaling pathway
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