龙牡汤对特应性皮炎小鼠树突状细胞IgE高亲和力受体γ亚基启动子序列DNA甲基化水平调控的研究

项目名称： 龙牡汤对特应性皮炎小鼠树突状细胞IgE高亲和力受体γ亚基启动子序列DNA甲基化水平调控的研究

项目编号： No.81503447

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 宋艳丽

作者单位： 中国中医科学院西苑医院

项目金额： 17万元

中文摘要： 特应性皮炎(AD)是一种遗传、免疫和环境等因素相互作用的炎症性皮肤病，其确切的发病机制尚未完全明了，AD患者皮肤和血液中的树突状细胞特征性高表达IgE高亲和力受体(FcεRⅠ)在AD炎症的产生和控制中发挥关键作用。有研究发现AD患者树突状细胞FcεRⅠγ亚基基因调节序列甲基化水平低下，导致FcεRⅠγ亚基与FcεRⅠ在细胞表面过度表达，从而参与疾病的发病过程。我们课题组前期研究发现龙牡汤治疗AD有较好的临床疗效（有效率83.4%），明显改善患者的临床症状，减少复发，提高生活质量，无明显毒副作用，同时可降低AD患者血清中IgE的表达。因此我们构想龙牡汤是否能够提高Nc/Nga鼠树突状细胞FcεRⅠγ亚基基因调节序列甲基化水平，进而抑制FcεRⅠγ亚基与FcεRⅠ在细胞表面过度表达，降低IgE水平，从而达到治疗作用？首次从表观遗传学角度探讨龙牡汤治疗AD的机制。

中文关键词： 特应性皮炎；龙牡汤；IgE高亲和力受体γ亚基；DNA甲基化；树突状细胞

英文摘要： Environmental factors influencing the manifestation of atopic diseases, which imply epigenetic modification of key genes may contribute to the pathogenesis of atopic disease.The high-affinity receptor for IgE FcεRⅠis strongly up regulated on dendritic cells from atopic donors and involved in the pathophysiology of atopic disease.It was proved that compared with the healthy controls, the DNA methylation levels are reduced and the levels of FcεRⅠγand surface FcεRⅠγ expression in monoeytes are increased in AD Patients. DNA hypomethylation leads to FcεRⅠγsubunit and surface FcεRⅠover expression in atopic dermatitis.We have found that Longmu solution is effective in the treatment of AD. It could improve the clinical symptom （83.4% effective rate）, reduce recurrence, enhance the quality of life, no obvious side effect and reduce the expression of IgE in serum. So, we composed that DNA Methylation is enhanced in atopic dermatitis NC/Nga mice treated by Longmu solution and the level of FcεRⅠγ gene and FcεRⅠ expression are reduced in the treatment of AD. For the first time the mechanisms of treatment is revealed during the treatment of AD with Longmu solution from the point of view of epigenetics.

英文关键词： atopic dermatitis;LongMu solution;FcεRⅠγ chain;DNA methylation;dentritic cells