DHA在缓解自身性免疫疾病EAE中的作用及机制研究

发布时间：2018-05-14 08:46

本文选题：Docosahexaenoic + acid　；参考：《华东师范大学》2017年硕士论文

【摘要】：免疫系统错误的将自身正常细胞识别为抗原,进行细胞免疫和/或体液免疫,使机体组织受到损伤,这样的疾病称为自身免疫疾病。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发生机制对于疾病的预防,诊断和治疗都有重要作用。EAE是被广泛用于研究多发性硬化症的动物模型。多不饱和脂肪酸在人体内不能自身合成,主要来源是从食物中获得。多不饱和脂肪酸对细胞生物膜和细胞的多种功能都有重要的作用,所以多不饱和脂肪酸对于哺乳动物是十分必需的。在已有的研究中,长链n-3多不饱和脂肪酸在免疫调节中具有重要的作用。其中长链n-3多不饱和脂肪酸在人体和动物模型中都证实能够减弱T细胞介导的炎症应答。二十二碳六烯酸(Docosahexaenoic acid,DHA)对多种炎症性疾病有一定的治疗效果,如动脉粥样硬化、哮喘、关节炎。DHA在多发性硬化症中抑制炎症的具体分子机制还不是特别清楚,而且透彻了解EAE疾病的病理学机制有助于对多发性硬化症的预防和治疗。我们通过给小鼠喂食DHA后,用MOG免疫EAE模型并观察其临床发病。我们发现喂食DHA后小鼠的炎症反应减轻。检测炎症因子的分泌也得到同样的结果。树突状细胞在炎症反应中的作用主要是起始反应、激活初始T细胞、发挥吞噬细胞作用清除病原体。EAE模型中,检测DHA处理后树突状细胞对特异性的T细胞活化,发现树突状细胞对T细胞激活的能力不同,树突状细胞的共刺激因子表达和细胞因子表达都有显著差异。我们在体外分化的树突状细胞也证实了 DHA促进调节树突状细胞的分化功能。将体外受DHA刺激分化得来的树突状细胞通过过继实验并诱导EAE,其临床表现和喂食DHA的EAE小鼠发病一致。我们可以得出DHA通过调节树突状细胞的功能,并增强了细胞的免疫耐受。GPR120又称FFA4R,是n-3多不饱和脂肪酸的受体。已有的研究发现GPRs与炎症反应有关。我们通过检测GPR120在树突状细胞分化的不同时期蛋白表达量,发现GPR120蛋白表达与树突状细胞的成熟呈现正相关关系。这提示我们GPR120在树突状细胞的分化中发挥功能。
[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.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R744.51

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