海洋甾体化合物YC-5对类风湿关节炎的治疗作用及其初步机制研究

发布时间：2018-07-06 11:28

本文选题：海洋甾体类化合物YC-5 + 类风湿关节炎　；参考：《桂林医学院》2017年硕士论文

【摘要】：目的:本研究以海洋甾体化合物YC-5为研究对象,探讨其抗炎、止痛等药效学作用,并探讨其对类风湿关节炎的治疗作用及其初步作用机制。方法:(1)YC-5对体内炎症模型的影响:通过二甲苯致小鼠耳廓肿胀实验、大鼠棉球肉芽肿实验,研究海洋甾体化合物YC-5对体内急慢性炎症模型的作用;(2)YC-5对体内疼痛模型的影响:通过热刺激实验、醋酸致小鼠扭体反应实验,研究YC-5对体内疼痛模型的影响;(3)YC-5对大鼠胶原诱导性关节炎(Collagen Induced Arthritis,CIA)模型的影响:通过建立胶原诱导性大鼠CIA模型,探讨YC-5对CIA大鼠关节炎评分指数的影响及对踝关节组织病理变化的作用;(4)YC-5抗RA的作用机制研究:通过ELISA、免疫荧光等实验,初步探讨YC-5对SD大鼠NF-κB信号网络相关炎症因子及氧化应激水平的影响。结果:(1)YC-5能明显抑制二甲苯所致小鼠耳廓肿胀(F=8.65,P0.01)以及棉球所致的大鼠肉芽肿(F=30.31,P0.01);(2)YC-5显著抑制热刺激所致疼痛(F=55.37,P0.01),并能明显延长扭体反应的潜伏期(F=25.03,P0.01),同时减少扭体次数(F=23.84,P0.01);(3)YC-5明显降低胶原诱导性关节炎的关节指数评分(F=546.95,P0.01),并减少踝关节中滑膜组织的增生及炎性细胞浸润;(4)YC-5显著降低病变滑膜组织中NF-κB p65的表达(F=76.77,P0.01),并显著降低血清炎症因子TNF-α(F=157.17,P0.01)、IL-1β(F=100.13,P0.01)、PGE2(F=164.48,P0.01)的表达水平;同时提高血清SOD的活力(F=14.42,P0.01),降低血清MDA的表达水平(F=22.92,P0.01);结论:海洋甾体化合物YC-5具有抗类风湿关节炎的作用,其可能机制是YC-5通过调节NF-κB信号网络相关炎症因子的水平,使炎性物质的释放减少,并使氧化应激反应减轻,同时改善滑膜炎症。这表明YC-5可能成为一种潜在的治疗类风湿关节炎的药物。
[Abstract]:Objective: to investigate the anti-inflammatory and analgesic effects of marine steroid YC-5 and its therapeutic effect on rheumatoid arthritis. Methods: (1) the effect of YC-5 on the inflammatory model in vivo: the mouse auricle swelling induced by xylene and the rat cotton ball granuloma test were used. To study the effect of marine steroid YC-5 on acute and chronic inflammatory model in vivo. (2) the effect of YC-5 on pain model in vivo. To study the effect of YC-5 on the pain model in vivo. (3) the effect of YC-5 on the collagen induced arthritis (CIA) model in rats. To investigate the effect of YC-5 on the arthritis score index of CIA rats and the pathological changes of ankle tissue. (4) the mechanism of YC-5 anti-RA: by ELISA-immunofluorescence assay. To investigate the effects of YC-5 on NF- 魏 B signaling network related inflammatory factors and oxidative stress in SD rats. Results: (1) YC-5 could significantly inhibit the auricle swelling induced by xylene in mice (FJ 8.65 P0.01) and the rat granuloma induced by cotton balls (F30.31 P0.01); (2) YC-5 significantly inhibited the pain induced by heat stimulation (FN 55.37 P0.01), prolonged the latent period of writhing reaction (F25.03 P0.01), and reduced the number of writhing bodies (F23.84 P0.01); (3) YC-5. (4) YC-5 significantly decreased the expression of NF- 魏 B p65 and IL-1 尾 (FF157.17P0.01) and IL-1 尾 (FF100.13P0.01) in the synovial tissues of the patients with synovial lesions (P 0.01), and decreased the expression of NF- 魏 B p65 in the synovial tissues of the patients with collagen induced arthritis (P0.01), and decreased the proliferation of synovial tissue and the infiltration of inflammatory cells in the ankle joint. (4) YC-5 significantly decreased the expression of NF- 魏 B p65 in the synovial tissues (FF76.7 P0.01) and the expression of IL-1 尾 (FF100.13P0.01) in the serum inflammatory factor TNF- 伪 (FN157.17P0.01). At the same time, the activity of serum SOD was increased (FN 14.42 P0.01) and the level of serum MDA was decreased (FH22.92 P0.01) conclusion: Marine steroidal compound YC-5 has the effect of anti-rheumatoid arthritis, and its possible mechanism is that YC-5 regulates the level of inflammatory factors associated with NF- 魏 B signaling network. Reduce the release of inflammatory substances, reduce oxidative stress, and improve synovitis. This suggests that YC-5 may be a potential treatment for rheumatoid arthritis.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22

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