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中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (9): 966-971.

• 基础研究 • 上一篇    下一篇

牛膝总皂苷对大鼠急性痛风性关节炎的防治作用及机制研究

那 莎1,段陈方圆2,王 璐1,吕 磊1,陈光亮1   

  1. 1安徽中医药大学中西医结合学院,合肥 230038,安徽;2澳门科技大学中医药学院,澳门
  • 收稿日期:2017-07-13 修回日期:2017-08-16 出版日期:2017-09-26 发布日期:2017-09-30
  • 通讯作者: 陈光亮,男,博士,教授,博士生导师,研究方向:药物防治代谢性疾病。 E-mail:chguangl@163.com
  • 作者简介:那莎,女,硕士,讲师,研究方向:药物防治代谢性疾病。 E-mail:nasha022@163.com
  • 基金资助:

    国家自然科学基金资助项目(81573670)

Effects and mechanism of total saponins of Achyranthes on acute gouty arthritis in rats

NA Sha 1, DUAN Chenfangyuan 2, WANG Lu 1, LV Lei 1, CHEN Guangliang 1   

  1. 1 Clinical College of Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui, China, 2 School of Chinese Medicine, Macau University of Science and Technology, Macau, China
  • Received:2017-07-13 Revised:2017-08-16 Online:2017-09-26 Published:2017-09-30

摘要:

目的: 研究牛膝总皂苷(total saponin Achyranthes,TSA)对大鼠急性痛风性关节炎(acute gouty arthritis, AGA)的防治作用及其机制。方法: 雄性SD大鼠随机分为正常组,模型组,TSA高、中、低剂量组(200、60、20 mg·kg-1·d-1)以及吲哚美辛组(5 mg·kg-1·d-1),灌胃给药,每天2次,连续5 d,第3天除正常组外,大鼠踝关节腔内注射尿酸钠溶液,测定大鼠关节肿胀度,48 h后处死大鼠,检测大鼠肿胀关节浸出液IL-1β、IL-18、IL-6水平,以及踝关节病理组织学,免疫组化法检测大鼠踝关节IL-1β的表达,Western blot法检测滑膜组织中NALP3(NACHT, LRR and PYD domains-containing protein 3)炎性体相关蛋白变化。结果: 模型组大鼠关节显著肿胀,活动减少,关节浸出液IL-1β、IL-6和IL-18水平显著增高,关节滑膜组织增生,炎性细胞浸润明显,IL-1β蛋白表达增加,滑膜组织NALP3、凋亡相关斑点样蛋白(ASC)、caspase-1前体和活性形式蛋白表达增高。TSA高、中剂量及吲哚美辛组大鼠上述指标均不同程度改善。 结论: TSA对AGA有防治作用,其机制可能是抑制NALP3炎性体装配和激活以及抑制炎性细胞因子的表达。

关键词: 牛膝总皂苷, 急性痛风性关节炎, 防治作用, 机制

Abstract:

AIM: To study the preventive effect and mechanism of total saponins of Achyranthes (TSA) on acute gouty arthritis (AGA) in rats. METHODS: Male SD rats were randomly divided into the normal group, model group, TSA high, medium and low dose group (200, 60, 20 mg·kg-1·d-1) and indomethacin group (5 mg·kg-1·d-1).All groups received oral administration, 2 times a day, for 5 consecutive days.Uric acid sodium solution was injected into the rat ankle joint cavity on the third day except the normal group to determine the degree of rat joint swelling. The rats were sacrificed at 48 hours after the injection to detect the IL-1β, IL-18 and IL-6 levels in rat joint swelling leaching solution, and ankle pathology was performed thereafter. The expression of IL-1β protein in the ankle joint of rats was detected by immunohistochemistry. The levels of NALP3 (NACHT, LRR and PYD domains-containing protein 3) and inflammatory related proteins were detected by Western blot. RESULTS: Compared with the normal group, the rats in the model group were significantly swollen, less active. Synovial tissue hyperplasia and inflammatory cell infiltration were observed in synovial joints, the expression of IL-1β protein increased.The levels of IL-1β, IL-18 and IL-6 in synovial fluid, and the NALP3, ASC, pro-caspase-1 and cleaved caspase-1 in synovial tissue were increased significantly. The above indexes in the high and middle dose group and the indomethacin group were improved to different degree. CONCLUSION: TSA has an obvious preventive and therapeutic effect on AGA, and the mechanism may be related with suppressing the NALP3 inflammasome activation and inhibiting the cytokines production.

Key words: total saponin Achyranthes, acute gouty arthritis, preventive effect, mechanism

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