木犀草素抗骨關(guān)節(jié)炎的作用機(jī)制研究
本文選題:木犀草素 + 骨關(guān)節(jié)炎; 參考:《蘇州大學(xué)》2015年博士論文
【摘要】:骨關(guān)節(jié)炎(osteoarthritis,OA),又稱退行性骨關(guān)節(jié)病,是一種多發(fā)生于中老年人并以關(guān)節(jié)軟骨的變性、破壞及骨質(zhì)增生為特征的慢性關(guān)節(jié)病。木犀草素是一種天然黃酮類化合物,存在于多種蔬菜和藥用植物中,其藥理活性涉及抗氧化、抗炎、抗腫瘤、神經(jīng)保護(hù)以及對(duì)血管的作用等方面。本文從整體動(dòng)物和細(xì)胞水平層面上,探討了木犀草素抗骨關(guān)節(jié)炎的作用機(jī)制,論文分為以下兩個(gè)部分:第一部分木犀草素抗骨關(guān)節(jié)作用機(jī)制研究采用弗氏佐劑建立大鼠骨關(guān)節(jié)炎來評(píng)價(jià)木犀草素抗骨關(guān)節(jié)炎的作用,通過檢測(cè)相關(guān)指標(biāo),包括腳腫脹體積、關(guān)節(jié)指數(shù)、血及滑膜液中白細(xì)胞及中性粒細(xì)胞數(shù)值、血清中炎癥因子白介素-6(IL-6)、白介素-1β(IL-1β)、腫瘤壞死因子α(TNF-α)、Th1/Th2平衡、Th17/Treg平衡及P2X4信號(hào)通路并來評(píng)價(jià)木犀草素的抗骨關(guān)節(jié)炎作用,結(jié)果顯示,木犀草素各劑量組均能顯著減低骨關(guān)節(jié)炎大鼠腳腫脹體積,關(guān)節(jié)炎指數(shù),血及滑膜液中白細(xì)胞及中性粒細(xì)胞數(shù)值,血清中炎癥因子IL-6、IL-1β、TNF-α,調(diào)節(jié)Th1/Th2平衡、Th17/Treg平衡,抑制P2X4信號(hào)通路,結(jié)果顯示木犀草素具有抗骨關(guān)節(jié)炎作用。第二部分木犀草素抗骨關(guān)節(jié)炎的細(xì)胞機(jī)制研究采用LPS-誘導(dǎo)巨噬細(xì)胞激活模型來評(píng)價(jià)木犀草素抗炎作用,通過檢測(cè)相關(guān)指標(biāo),包括NO,IL-6,IL-1β,TNF-α,i NOS,MAPK/NF-кB信號(hào)通路P2X4信號(hào)通路,結(jié)果顯示,木犀草素夠抑制LPS-誘導(dǎo)巨噬細(xì)胞激活,說明木犀草素能對(duì)抗炎癥的發(fā)生,從而抗骨關(guān)節(jié)炎。
[Abstract]:Osteoarthritis (OA), also known as degenerative osteoarthropathy, is a chronic arthropathy characterized by degeneration, destruction and hyperosteogenesis of articular cartilage. Luteolin is a kind of natural flavonoids found in many kinds of vegetables and medicinal plants. Its pharmacological activities are related to antioxidant, anti-inflammatory, anti-tumor, neuroprotective and vascular effects. In this paper, the mechanism of luteolin against osteoarthritis was studied on the level of whole animal and cell. The thesis is divided into two parts as follows: the first part is the mechanism of luteolin anti-osteoarthritis in rats. The effect of luteolin on osteoarthritis was evaluated by using Freund's adjuvant to evaluate the effect of luteolin on osteoarthritis. Joint index, leukocytes and neutrophils in blood and synovial fluid, serum inflammatory cytokines interleukin-6 (IL-6), interleukin-1 尾 (IL-1 尾), tumor necrosis factor- 偽 (TNF- 偽), Th1 / Th2 balance Th17 / Treg balance and P2X4 signaling pathway were used to evaluate the anti-osteoarthritis effect of luteolin. The results showed that luteolin could significantly reduce the swelling volume of foot, arthritis index, leukocyte and neutrophils in blood and synovial fluid, IL-6, IL-1 尾 and TNF- 偽, and regulate Th1 / Th2 balance and Th17 / Treg balance in rats with osteoarthritis. The inhibitory effect of luteolin on osteoarthritis was found by inhibiting P2X 4 signaling pathway. The second part of the study on the cellular mechanism of luteolin anti-osteoarthritis was to evaluate the anti-inflammatory effect of luteolin by using LPS-induced macrophage activation model. The results showed that luteolin could be used to evaluate luteolin's anti-inflammatory effect by detecting some related indexes, including the signal pathway P2X4 of NO-IL-6, IL-1 尾, TNF- 偽 and NOSN-MAPK / NF-B signaling pathway. Luteolin can inhibit LPS- induced macrophage activation, suggesting that luteolin can prevent inflammation and thus osteoarthritis.
【學(xué)位授予單位】:蘇州大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2015
【分類號(hào)】:R684.3
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