金荞麦抗类风湿性关节炎药理作用研究
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摘要
金荞麦，Fagopyrum cymosum (Trey.) Meisn，为蓼科荞麦属植物的干燥根茎，别名苦荞麦、野荞麦、天荞麦、开金锁、苦荞头等，主要分布在我国东北、西北、华北、西南一带的高寒山区。金荞麦，块茎入药，性凉，味辛、苦，是我国民间常用的一味中草药，具有清热解毒、活血化瘀、清肺排痰，排脓消肿，祛风化湿的功效。
尽管金荞麦在民间以单药或配方用于治疗类风湿性关节炎（rheumatoidarthritis，RA），并获得显著疗效，但是国内外目前尚无对其有效成分抗RA的基础研究，相关的分子机制更未能阐明。本课题拟利用民族药金荞麦，采用佐剂性关节(adjuvant arthritis, AA)大鼠模型、疼痛动物模型，对金荞麦抗类风湿性关节炎作用及机理进行了研究，并筛选出其抗类风湿性关节炎有效部位，为以后开发金荞麦研制抗类风湿新药提供实验依据。本课题的主要研究内容包括以下四个方面：
1.采用大鼠佐剂关节炎模型，从AA大鼠足爪肿胀度、多发关节炎评分、体重及免疫器官的变化、病理组织学、血液流变性及对血清中前炎症因子白细胞介素-1(interleukin-1，IL-1)和TNF-α肿瘤坏死因子-α (tumor necrosis factor-α，TNF-α)的水平这几个方面来考察金荞麦抗RA作用与机理。研究表明金荞麦乙醇总浸膏可以改善AA大鼠的足爪肿胀及多发性关节炎现象，并可恢复AA大鼠细胞免疫功能，金荞麦能够有效治疗RA，同时金荞麦还可改善血液流变学的异常变化和明显抑制AA大鼠血清中前炎症因子IL-1和TNF-α的水平，提示这有可能是其抗RA作用机制。
2.采用AA动物模型对金荞麦抗RA有效部位进行系统筛选，初步证实金荞麦RA的有效成分可能集中于氯仿提取部位，其有可能通过降低IL-1和TNF-α的水平起到抗RA作用。
3.从对佐剂大鼠的Thl／Th2平衡状态的影响探讨金荞麦氯仿部位抗RA的作用机制。结果发现氯仿组金荞麦浸膏能明显减轻AA大鼠继发性病变，抑制血管翳生成、滑膜增殖及软骨破坏的作用机制可能与其降低血中IFN-γ，升高IL-4的含量，从而使Th1/Th2失衡状态趋向平衡，增强细胞免疫功能有关。
4.采用小鼠热板法、醋酸致小鼠扭体反应以及致痛等动物模型考察金荞麦镇痛作用。结果证实，金荞麦具有较好的镇痛作用，能够降低局部炎症组织中前列腺素E (PGE2)含量，这可能是其发挥镇痛作用的机制。
Fagopyrum cymosum (Trey.) Meisn is the dry root of a species of genusFagopyrum (Polygonaceae), which grows mainly in southwester, northeast, andnorthwest in China. As the most widely distributed wild species and has aresource-rich. Its rhizome was regarded as a folk medicine in China to treat variousailments of the lung, dysentery and rheumatism. However, no in vivo study on thetherapeutic effects of Fagopyrum cymosum (Trey.) Meisn for Rheumatoid Arthritis(RA) has been reported and the detailed mechanisms of action have not beenunderstood.
The aims of the current study were to identify the most efftive extracts from therhizomes of Fagopyrum cymosum in the adjuvant arthritis (AA) model and painmodel, and to further investigate the possible underlying mechanisms. The studywould provide experimental basis for the development of Fagopyrum cymosum (Trey.)Meisn into an anti-rheumatic drug. The study included four parts:
1. An evaluation system with arthritis damage, index of immune organs,histopathological and hematological parameters was employed in the study, and thepossible underlying mechanisms in which some pro-inflammatory cytokines IL-1andTNF-α are involved were further investigated in the AA model. Taken together, thefindings of this study demonstrated profound therapeutic effects of extract ofFagopyrum cymosum on AA. It directs towards the control of arthritis progression andprevents synovial proliferation, cartilage and bone destruction of the arthritic joints ofAA rats. In addition, EFC changes the hemorheological disorders and reduces thelevel of pro-inflammatory cytokines (IL-1and TNF-α).
2. The most effective extracts were identified in the in AAmodel. Taken together,all of these data demonstrated that EFC2(the Fagopyrum cymosum extracted from chloroform) posses anti-arthritic activities and may support the fact the traditionalapplication of this herb in treating various diseases associated with RA.
3. In order to explore the anti-RA mechanism of EFC2, the balance of Thl/Th2inAA rats with the treatment of EFC2was examined. EFC2significantly reducedsecondary lesions in AA rats, inhibited pannus formation, and delayed synovialproliferation and cartilage destruction.The effect may be related to decrease level ofIFN-γ and increased level of IL-4in the serum, which in turn correct the imbalance ofTh1/Th2and enhance cellular immune function.
4. The acetic acid-induced writhing response and hot plate pain model in micewere used to evaluate the analgesic effect of EFC. EFC had good anti-inflammatoryand analgesic properties, likely due to the reduced the level of prostaglandin E in localinflammatory tissue.
尽管金荞麦在民间以单药或配方用于治疗类风湿性关节炎（rheumatoidarthritis，RA），并获得显著疗效，但是国内外目前尚无对其有效成分抗RA的基础研究，相关的分子机制更未能阐明。本课题拟利用民族药金荞麦，采用佐剂性关节(adjuvant arthritis, AA)大鼠模型、疼痛动物模型，对金荞麦抗类风湿性关节炎作用及机理进行了研究，并筛选出其抗类风湿性关节炎有效部位，为以后开发金荞麦研制抗类风湿新药提供实验依据。本课题的主要研究内容包括以下四个方面：
1.采用大鼠佐剂关节炎模型，从AA大鼠足爪肿胀度、多发关节炎评分、体重及免疫器官的变化、病理组织学、血液流变性及对血清中前炎症因子白细胞介素-1(interleukin-1，IL-1)和TNF-α肿瘤坏死因子-α (tumor necrosis factor-α，TNF-α)的水平这几个方面来考察金荞麦抗RA作用与机理。研究表明金荞麦乙醇总浸膏可以改善AA大鼠的足爪肿胀及多发性关节炎现象，并可恢复AA大鼠细胞免疫功能，金荞麦能够有效治疗RA，同时金荞麦还可改善血液流变学的异常变化和明显抑制AA大鼠血清中前炎症因子IL-1和TNF-α的水平，提示这有可能是其抗RA作用机制。
2.采用AA动物模型对金荞麦抗RA有效部位进行系统筛选，初步证实金荞麦RA的有效成分可能集中于氯仿提取部位，其有可能通过降低IL-1和TNF-α的水平起到抗RA作用。
3.从对佐剂大鼠的Thl／Th2平衡状态的影响探讨金荞麦氯仿部位抗RA的作用机制。结果发现氯仿组金荞麦浸膏能明显减轻AA大鼠继发性病变，抑制血管翳生成、滑膜增殖及软骨破坏的作用机制可能与其降低血中IFN-γ，升高IL-4的含量，从而使Th1/Th2失衡状态趋向平衡，增强细胞免疫功能有关。
4.采用小鼠热板法、醋酸致小鼠扭体反应以及致痛等动物模型考察金荞麦镇痛作用。结果证实，金荞麦具有较好的镇痛作用，能够降低局部炎症组织中前列腺素E (PGE2)含量，这可能是其发挥镇痛作用的机制。
Fagopyrum cymosum (Trey.) Meisn is the dry root of a species of genusFagopyrum (Polygonaceae), which grows mainly in southwester, northeast, andnorthwest in China. As the most widely distributed wild species and has aresource-rich. Its rhizome was regarded as a folk medicine in China to treat variousailments of the lung, dysentery and rheumatism. However, no in vivo study on thetherapeutic effects of Fagopyrum cymosum (Trey.) Meisn for Rheumatoid Arthritis(RA) has been reported and the detailed mechanisms of action have not beenunderstood.
The aims of the current study were to identify the most efftive extracts from therhizomes of Fagopyrum cymosum in the adjuvant arthritis (AA) model and painmodel, and to further investigate the possible underlying mechanisms. The studywould provide experimental basis for the development of Fagopyrum cymosum (Trey.)Meisn into an anti-rheumatic drug. The study included four parts:
1. An evaluation system with arthritis damage, index of immune organs,histopathological and hematological parameters was employed in the study, and thepossible underlying mechanisms in which some pro-inflammatory cytokines IL-1andTNF-α are involved were further investigated in the AA model. Taken together, thefindings of this study demonstrated profound therapeutic effects of extract ofFagopyrum cymosum on AA. It directs towards the control of arthritis progression andprevents synovial proliferation, cartilage and bone destruction of the arthritic joints ofAA rats. In addition, EFC changes the hemorheological disorders and reduces thelevel of pro-inflammatory cytokines (IL-1and TNF-α).
2. The most effective extracts were identified in the in AAmodel. Taken together,all of these data demonstrated that EFC2(the Fagopyrum cymosum extracted from chloroform) posses anti-arthritic activities and may support the fact the traditionalapplication of this herb in treating various diseases associated with RA.
3. In order to explore the anti-RA mechanism of EFC2, the balance of Thl/Th2inAA rats with the treatment of EFC2was examined. EFC2significantly reducedsecondary lesions in AA rats, inhibited pannus formation, and delayed synovialproliferation and cartilage destruction.The effect may be related to decrease level ofIFN-γ and increased level of IL-4in the serum, which in turn correct the imbalance ofTh1/Th2and enhance cellular immune function.
4. The acetic acid-induced writhing response and hot plate pain model in micewere used to evaluate the analgesic effect of EFC. EFC had good anti-inflammatoryand analgesic properties, likely due to the reduced the level of prostaglandin E in localinflammatory tissue.
引文
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