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维药刺山柑抗类风湿性关节炎作用的研究

Study on the Action of Capparis Spinosa L. Against of Rheumatoid Arthritis

【作者】 高莹莹

【导师】 余龙江; 敖明章;

【作者基本信息】 华中科技大学 , 生物化学与分子生物学, 2007, 硕士

【摘要】 刺山柑Capparis Spinosa L.为白花菜科山柑属植物,源于亚洲中西部干旱地区。我国新疆、西藏境内广有分布,在当地是一种常用的民族传统药物,用于治疗痛风,类风湿性关节炎(rheumatoid arthritis,RA)等。本文研究了刺山柑对多种非特异性炎症模型、疼痛动物模型以及小鼠免疫功能的影响;并进一步建立特异性佐剂关节炎大鼠模型,采用放射免疫、荧光分光等技术对刺山柑抗类风湿性关节炎作用及机理进行了研究,为以后开发刺山柑研制抗类风湿新药提供实验依据。(1)采用炎症药物筛选常用动物模型对刺山柑进行系统筛选,初步证实刺山柑抗炎有效成分可能集中于醚提部位和醇提部位。(2)采用二甲苯致小鼠耳廓肿胀及皮肤毛细血管通透性增高、角叉菜胶致小鼠足跖肿胀、醋酸致小鼠扭体反应以及小鼠热板致痛多种动物模型进行整体药效实验。结果证实,刺山柑具有较好的抗炎镇痛作用,降低局部炎症组织前列腺素E2(PGE2)含量可能是其重要作用机制。(3)采用小鼠碳粒廓清实验和二硝基氟苯(dinitrofluorobenzene,DNFB)致小鼠迟发型过敏反应(delayed type hypersensitivity,DTH)反应实验从免疫功能调节角度研究刺山柑提取物对小鼠免疫功能的影响,结果证实刺山柑提取物具有一定的抑制免疫系统功能的作用,对小鼠血管网状内皮系统的吞噬功能抑制作用较强。(4)采用大鼠佐剂关节炎模型研究刺山柑抗RA作用与机理。结果证实刺山柑对实验性动物关节炎模型(大鼠佐剂性关节炎adjuvant arthritis,AA)动物病理改变有明显改善作用,能够抑制弗氏完全佐剂引起的大鼠原发性足跖肿胀和继发性足跖肿胀;降低局部炎症组织炎症介质组胺(histamine,HA)、5-羟色胺(5-hydroxytryptamine ,5-HT )含量以及下调血清炎性细胞因子白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)可能是其抗RA的主要机制。

【Abstract】 Capparis Spinosa L. belongs to the plant family of Capparidaceae and Genus is Capparis. It probably originated from dry regions in west or central Asia. In our country, it is mainly distributed throughout Xinjiang and Tibet, and is used as a folk medicine in the districts. The herbal is widely used in the treatment of rheumatoid arthritis and gout in Xinjiang and Tibet. This paper was conducted to investigate the effect of Capparis Spinosa extract on non-specific inflammation models, pain models and immune function in mice. Moreover, the adjuvant arthritis model was adopted to investigate the pharmacological effects and mechanism of Capparis Spinosa extract on rheumatoid arthritis by means of advanced modern scientific research methods such as radioimmunoassay, ultraviolet spectrophotometry and fluorescence spectrophotometry. The results will provide experimental evidences for Capparis Spinosa’s development in the future.(1) The herbal was screened systematically by using the classical inflammation and painmodels for effective sites. The results showed the effective components may be contained in the aether extracts and ethanol extracts.(2) The activities of Capparis Spinosa extracts were tested by several types of models, including auris edema and increased vascular permeability induced by dimethylbenzene in mice, paw edema caused by carrageenin in mice, writhing reaction induced by acetic acid in mice and pain threshold induce by hot plate method in mice. The results showed the extracts of Capparis Spinosa L fruits has great ant-inflammatory and analgestic action, and inhibiting the synthesize or release of PGE2 in inflammatory tissue might be the major mechanism(3) Carbon clearance test and dinitrofluorobenzene-induced delayed type hypersensitivity test(DTH)were used to evaluate the immunomodulating effects of Capparis spinosa extract on non-specific and specific immunologic function in mice. The results showed Capparis Spinosa extracts could inhibited phagocytosis of Mononuclear macrophage in mice. (4) The pharmacological effects and mechanism of Capparis Spinosa extract on rheumatoid arthritis was investigated by using the adjuvant arthritis model. The results showed Capparis Spinosa extracts could improved the pathological changes in AA rats .It could the primary paw swelling and the secondary hind paw swelling in AA rats . Reducing the content of HA and 5-HT in inflammatory tissue as well as serum level of IL-1βand TNF-αmight be the major mechanism.

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