基于内质网应激通路探讨金铁锁醇提物治疗类风湿性关节炎的机制

    Exploring the Mechanism of Psammosilenes Radix Ethanolic Extract in Treating Rheumatoid Arthritis Based on the Endoplasmic Reticulum Stress Pathway

    • 摘要:
      目的  研究云南民间治疗风湿痹症常用药金铁锁在现代治疗类风湿性关节炎(rheumatoid arthritis,RA)中的应用,探索金铁锁醇提物的作用机制。
      方法 采用胶原诱导的RA小鼠模型,按照各给药组剂量连续给药21 d,并进行足肿胀和关节炎评分,组织病理学染色;ELISA检测小鼠血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的含量;Western blotting测定小鼠踝关节中转录激活因子6(activating transcription factor 6,ATF-6)、葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)、C/EBP同源蛋白(C/EBP-homologous protein antibody,CHOP)的表达;实时荧光定量核酸扩增检测细胞中ATF-6、GRP78、CHOP的mRNA表达。
      结果 各给药组显著降低了胶原诱导的RA小鼠的足肿胀、关节炎评分以及血清中促炎因子TNF-α的含量(P<0.01),组织病理学检查结果表明,各给药组改善了胶原诱导的RA小鼠的关节损伤,减少了膝关节炎性细胞浸润,踝关节ATF-6、GRP78蛋白及mRNA的表达显著降低(P<0.01),CHOP蛋白及mRNA的表达显著升高(P<0.05)。
      结论 通过调控内质网应激通路降低RA小鼠炎症反应可能是金铁锁改善RA滑膜炎症的潜在机制。

       

      Abstract:
      OBJECTIVE To investigate the application of Psammosilenes Radix(a commonly used traditional Chinese medicinal herb in Yunnan folk medicine for treating rheumatic arthralgia) in modern treatment of rheumatoid arthritis(RA), and to explore the mechanism of action of its ethanol extract.
      METHODS  collagen-induced RA mouse model was used, and the dosage of each administration group was continuously administered for 21 d. Foot swelling and arthritis scores, histopathological staining, and ELISA were used to detect the tumor necrosis factor-α(TNF-α) content in mouse serum. Western blotting was used to determine the expression of activator of transcription factor 6(ATF-6), glucose-regulated protein 78(GRP78), and C/EBP homologous protein(CHOP) proteins in mouse ankle joints; real-time fluorescence quantitative nucleic acid amplification detected the mRNA expression of ATF-6, GRP78, and CHOP in cells.
      RESULTS  Each administration group significantly reduced foot swelling, arthritis scores, and serum pro-inflammatory factor TNF-α content in collagen-induced RA mice(P<0.01), histopathological examination results showed that each administration group improved the joint damage of collagen-induced RA mice, reduced knee arthritic cell infiltration, and the expression of ATF-6 and GRP78 protein and mRNA in the ankle joint Significantly reduced(P<0.01), CHOP protein and mRNA expression significantly increased(P<0.05).
      CONCLUSION  It is suggested that reducing the inflammatory response in RA mice by regulating the endoplasmic reticulum stress pathway may be the potential of Psammosilenes Radix to improve RA synovial inflammation mechanism.

       

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