本文選題：Docosahexaenoic + acid��； 參考：《華東師范大學(xué)》2017年碩士論文

【摘要】：免疫系統(tǒng)錯誤的將自身正常細(xì)胞識別為抗原,進(jìn)行細(xì)胞免疫和/或體液免疫,使機(jī)體組織受到損傷,這樣的疾病稱為自身免疫疾病。自身免疫疾病的危害不言而喻,所以,研究各自身免疫疾病的發(fā)生機(jī)制對于疾病的預(yù)防,診斷和治療都有重要作用。EAE是被廣泛用于研究多發(fā)性硬化癥的動物模型。多不飽和脂肪酸在人體內(nèi)不能自身合成,主要來源是從食物中獲得。多不飽和脂肪酸對細(xì)胞生物膜和細(xì)胞的多種功能都有重要的作用,所以多不飽和脂肪酸對于哺乳動物是十分必需的。在已有的研究中,長鏈n-3多不飽和脂肪酸在免疫調(diào)節(jié)中具有重要的作用。其中長鏈n-3多不飽和脂肪酸在人體和動物模型中都證實能夠減弱T細(xì)胞介導(dǎo)的炎癥應(yīng)答。二十二碳六烯酸(Docosahexaenoic acid,DHA)對多種炎癥性疾病有一定的治療效果,如動脈粥樣硬化、哮喘、關(guān)節(jié)炎。DHA在多發(fā)性硬化癥中抑制炎癥的具體分子機(jī)制還不是特別清楚,而且透徹了解EAE疾病的病理學(xué)機(jī)制有助于對多發(fā)性硬化癥的預(yù)防和治療。我們通過給小鼠喂食DHA后,用MOG免疫EAE模型并觀察其臨床發(fā)病。我們發(fā)現(xiàn)喂食DHA后小鼠的炎癥反應(yīng)減輕。檢測炎癥因子的分泌也得到同樣的結(jié)果。樹突狀細(xì)胞在炎癥反應(yīng)中的作用主要是起始反應(yīng)、激活初始T細(xì)胞、發(fā)揮吞噬細(xì)胞作用清除病原體。EAE模型中,檢測DHA處理后樹突狀細(xì)胞對特異性的T細(xì)胞活化,發(fā)現(xiàn)樹突狀細(xì)胞對T細(xì)胞激活的能力不同,樹突狀細(xì)胞的共刺激因子表達(dá)和細(xì)胞因子表達(dá)都有顯著差異。我們在體外分化的樹突狀細(xì)胞也證實了 DHA促進(jìn)調(diào)節(jié)樹突狀細(xì)胞的分化功能。將體外受DHA刺激分化得來的樹突狀細(xì)胞通過過繼實驗并誘導(dǎo)EAE,其臨床表現(xiàn)和喂食DHA的EAE小鼠發(fā)病一致。我們可以得出DHA通過調(diào)節(jié)樹突狀細(xì)胞的功能,并增強(qiáng)了細(xì)胞的免疫耐受。GPR120又稱FFA4R,是n-3多不飽和脂肪酸的受體。已有的研究發(fā)現(xiàn)GPRs與炎癥反應(yīng)有關(guān)。我們通過檢測GPR120在樹突狀細(xì)胞分化的不同時期蛋白表達(dá)量,發(fā)現(xiàn)GPR120蛋白表達(dá)與樹突狀細(xì)胞的成熟呈現(xiàn)正相關(guān)關(guān)系。這提示我們GPR120在樹突狀細(xì)胞的分化中發(fā)揮功能。
[Abstract]:The immune system mistakenly recognizes its normal cells as antigens, carries out cellular and / or humoral immunity, and causes tissue damage. Such diseases are called autoimmune diseases. The harm of autoimmune diseases is self-evident. Therefore, studying the pathogenesis of autoimmune diseases plays an important role in disease prevention, diagnosis and treatment. EAE is widely used to study multiple sclerosis animal model. Polyunsaturated fatty acids are not self-synthesized in the human body and are derived mainly from food. Polyunsaturated fatty acids play an important role in cell biofilm and cell functions, so polyunsaturated fatty acids are essential for mammals. In previous studies, long chain n-3 polyunsaturated fatty acids play an important role in immune regulation. Long-chain n-3 polyunsaturated fatty acids have been shown to attenuate the T cell mediated inflammatory response in both human and animal models. 22 Docosahexaenoic acid (DHA) has a certain therapeutic effect on many inflammatory diseases, such as atherosclerosis, asthma, arthritis, and the specific molecular mechanism of inhibiting inflammation in multiple sclerosis is not very clear. Furthermore, a thorough understanding of the pathological mechanism of EAE's disease may contribute to the prevention and treatment of multiple sclerosis. After feeding DHA to mice, we immunized EAE model with MOG and observed its clinical pathogenesis. We found that the inflammatory response was reduced in mice fed with DHA. The same results were obtained by detecting the secretion of inflammatory factors. The role of dendritic cells in inflammatory response is mainly initial response, activation of initial T cells, phagocytic scavenging effect of pathogens. EAE model. The specific T cell activation of dendritic cells treated with DHA was detected. It was found that the ability of dendritic cells to activate T cells was different, and the expression of costimulatory factors and cytokines in dendritic cells were significantly different. Our differentiation of dendritic cells in vitro also confirmed that DHA promotes the regulation of dendritic cell differentiation. The clinical manifestations of dendritic cells induced by DHA in vitro were consistent with those of EAE mice fed with DHA. We can conclude that DHA is the receptor of n-3 polyunsaturated fatty acids by regulating the function of dendritic cells and enhancing the immune tolerance of the cells. GPR120 is also called FFA4R. Previous studies have found that GPRs is associated with inflammation. By detecting the protein expression of GPR120 in different stages of dendritic cell differentiation, we found that there was a positive correlation between the expression of GPR120 protein and the maturation of dendritic cells. This suggests that our GPR120 plays a role in the differentiation of dendritic cells.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R744.51

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