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薯蓣皂苷对膝骨性关节炎模型大鼠的治疗效果及其机制研究
Therapeutic effect and mechanism of dioscin on knee osteoarthritis model rats
投稿时间:2023-11-17  修订日期:2024-05-01
DOI:
中文关键词:  膝骨性关节炎  薯蓣皂苷  Wnt/β-catenin信号通路  大鼠
英文关键词:Knee osteoarthritis  Dioscin  Wnt/β-catenin signaling pathway  Rat
基金项目:浙江省医药卫生科技计划项目(2022RC238)
作者单位邮编
徐天波 中国人民解放军联勤保障部队第九〇三医院 310000
刘德国  
顾增辉  
郑宇翔  
侯振海* 中国人民解放军联勤保障部队第九〇三医院 310000
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中文摘要:
      目的 探索薯蓣皂苷对膝骨性关节炎(KOA)大鼠治疗效果,并探讨其可能机制。方法 采用切断前交叉韧带离断法建立KOA大鼠模型,40只SD大鼠随机分为假手术组、KOA组、薯蓣皂苷低剂量组(50mg/kg)、薯蓣皂苷高剂量组(100mg/kg),各组10只大鼠,正常组、KOA组给予生理盐水灌胃, 薯蓣皂苷组给与薯蓣皂苷灌胃,每天1次,连续8周。治疗8周,进行疼痛评分、组织病理学观察,酶联免疫吸附试验(ELISA)法检测关节液内肿瘤坏死因子-α(TNF-α)、白介素1β(IL-1β)、白介素6(IL-6)含量,Westen blot法检测关节软骨组织内信号通路Wnt3a抗体(Wnt3a)、?β-连环蛋白(β-catenin)、 人基质金属蛋白酶13(MMP-13),糖原合成酶激酶3β(GSK-3β)、Ⅱ型胶原蛋白抗体(CollagenⅡ)蛋白表达水平。结果 与假手术组比较,KOA组刺激缩足反射潜伏期(TWL)、机械缩足反射阈值(MWT)明显升高(P<0.05),而薯蓣皂苷组TWL、MWT较KOA组明显降低(P<0.05);薯蓣皂苷组大鼠膝关节大体观察及组织病理改变较KOA组明显改善;KOA组关节液内炎症因子水平、关节软骨内Wnt3a、β-catenin、MMP-13蛋白表达水平较假手术组明显升高,GSK-3β、CollagenⅡ蛋白表达水平明显降低,而薯蓣皂苷治疗后,炎症因子水平及Wnt3a、β-catenin、MMP-1蛋白表达水平较KOA组明显降低,GSK-3β、CollagenⅡ蛋白表达水平明显升高,差异均具有统计学意义(P<0.05)。结论 薯蓣皂苷能减轻膝骨性关节炎疼痛和软骨退行性改变,抑制关节腔内炎症反应,维持软骨代谢平衡,可能通过调控Wnt/β-catenin信号通路有关。
英文摘要:
      Objective: To explore the effect of dioscin on the therapeutic effect of knee osteoarthritis (KOA) rats, and explore its possible mechanism. Methods: The KOA rat model was established by cutting the anterior cruciate ligament, 40 SD rats were randomly divided into the sham group, the KOA group, the dioscin low-dose (50 mg / kg)group and the dioscin high-dose (100 mg / kg) group, and 10 rats were assigned to each group, the sham group and the KOA group were administrated with normal saline by gavage,dioscin was administrated by gavage in the dioscin groups,once a day for 8 weeks.After 8 weeks of treatment, pain scores and histopathological observations were performed. Enzyme-linked immunosorbent assay (ELISA) method was used to detect the contents of tumor necrosis factor-α (TNF-α),interleukin-1 β( IL-1β) and interleukin-6(IL-6) in the joint fluid, and Western blot was used to detect the contents of WNT3a antigen (Wnt3a),recombinant beta catenin (β-catenin) ,human matrix metalloproteinase 13(MMP-13) and glycogen synthase kinase-3 beta(GSK-3β), Collagenase II(Collagen II) in the articular cartilage tissue.Results: Compared with the sham operation group, thermal withdrawal latency(TWL) and mechanical withdrawal threshold(MWT) of the KOA group were significantly increased (P<0.05), while the TWL and MWT of the dioscin groups were significantly lower than those of the KOA group (P<0.05); histopathological changes were significantly improved compared with those in the KOA group; the levels of inflammatory factors in the joint fluid, the protein expression levels of Wnt3a,β-catenin, and MMP-13 in the articular cartilage in the KOA group were significantly higher than those in the sham operation group, and the expression levels of GSK-3β and CollagenⅡ were significantly higher than those in the sham group. However, after dioscin treatment, the levels of inflammatory factors and the protein expression levels of Wnt3a,β-catenin, and MMP-1 were significantly lower than those in the KOA group, and the protein expression levels of GSK-3β and Collagen Ⅱ were significantly increased, and the differences were statistically significant ( P<0.05).Conclusion: Dioscin can relieve knee osteoarthritis pain and cartilage degenerative changes, inhibit the inflammatory response in the joint cavity, and maintain the balance of cartilage metabolism, which may be related to the regulation of Wnt/β-catenin signaling pathway.
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