本文選題：海洋甾體類(lèi)化合物YC-5 + 類(lèi)風(fēng)濕關(guān)節(jié)炎�。� 參考：《桂林醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:本研究以海洋甾體化合物YC-5為研究對(duì)象,探討其抗炎、止痛等藥效學(xué)作用,并探討其對(duì)類(lèi)風(fēng)濕關(guān)節(jié)炎的治療作用及其初步作用機(jī)制。方法:(1)YC-5對(duì)體內(nèi)炎癥模型的影響:通過(guò)二甲苯致小鼠耳廓腫脹實(shí)驗(yàn)、大鼠棉球肉芽腫實(shí)驗(yàn),研究海洋甾體化合物YC-5對(duì)體內(nèi)急慢性炎癥模型的作用;(2)YC-5對(duì)體內(nèi)疼痛模型的影響:通過(guò)熱刺激實(shí)驗(yàn)、醋酸致小鼠扭體反應(yīng)實(shí)驗(yàn),研究YC-5對(duì)體內(nèi)疼痛模型的影響;(3)YC-5對(duì)大鼠膠原誘導(dǎo)性關(guān)節(jié)炎(Collagen Induced Arthritis,CIA)模型的影響:通過(guò)建立膠原誘導(dǎo)性大鼠CIA模型,探討YC-5對(duì)CIA大鼠關(guān)節(jié)炎評(píng)分指數(shù)的影響及對(duì)踝關(guān)節(jié)組織病理變化的作用;(4)YC-5抗RA的作用機(jī)制研究:通過(guò)ELISA、免疫熒光等實(shí)驗(yàn),初步探討YC-5對(duì)SD大鼠NF-κB信號(hào)網(wǎng)絡(luò)相關(guān)炎癥因子及氧化應(yīng)激水平的影響。結(jié)果:(1)YC-5能明顯抑制二甲苯所致小鼠耳廓腫脹(F=8.65,P0.01)以及棉球所致的大鼠肉芽腫(F=30.31,P0.01);(2)YC-5顯著抑制熱刺激所致疼痛(F=55.37,P0.01),并能明顯延長(zhǎng)扭體反應(yīng)的潛伏期(F=25.03,P0.01),同時(shí)減少扭體次數(shù)(F=23.84,P0.01);(3)YC-5明顯降低膠原誘導(dǎo)性關(guān)節(jié)炎的關(guān)節(jié)指數(shù)評(píng)分(F=546.95,P0.01),并減少踝關(guān)節(jié)中滑膜組織的增生及炎性細(xì)胞浸潤(rùn);(4)YC-5顯著降低病變滑膜組織中NF-κB p65的表達(dá)(F=76.77,P0.01),并顯著降低血清炎癥因子TNF-α(F=157.17,P0.01)、IL-1β(F=100.13,P0.01)、PGE2(F=164.48,P0.01)的表達(dá)水平;同時(shí)提高血清SOD的活力(F=14.42,P0.01),降低血清MDA的表達(dá)水平(F=22.92,P0.01);結(jié)論:海洋甾體化合物YC-5具有抗類(lèi)風(fēng)濕關(guān)節(jié)炎的作用,其可能機(jī)制是YC-5通過(guò)調(diào)節(jié)NF-κB信號(hào)網(wǎng)絡(luò)相關(guān)炎癥因子的水平,使炎性物質(zhì)的釋放減少,并使氧化應(yīng)激反應(yīng)減輕,同時(shí)改善滑膜炎癥。這表明YC-5可能成為一種潛在的治療類(lèi)風(fēng)濕關(guān)節(jié)炎的藥物。
[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- 偽 (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.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R593.22

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