过敏体质理论及其外周血基因表达谱研究

【作者】 王睿林；

【导师】 王琦；

【作者基本信息】 北京中医药大学 ， 中医基础理论， 2009， 博士

【摘要】 目的对过敏体质的相关文献进行梳理,分析古代及现代对过敏体质的认识,补充中医体质学过敏体质相关理论;采用基因芯片技术,对过敏体质者的外周血基因表达谱进行研究,探讨过敏体质分子生物学特征,为过敏体质的辨识和防治,提供理论及实验依据。方法梳理分析古今文献中有关过敏体质的论述,在中医体质学对过敏体质的概念、成因、特征、诊断、干预方法论述的基础上,补充过敏体质的相关理论。在临床流行病学调查的基础上,按过敏体质标准,挑选30例平和体质者和15例过敏体质者,对其进行常规体检、中医症状体征调查。取上述受试者的外周血,提取总RNA并进行扩增和标记,用Sentrix(?) Human-6 Expression BeadChip检测受试样品,并将所得数据进行统计学分析,对差异表达基因进行GO注释和pathway分析,并对差异表达基因的生物学功能进行评价,阐述部分差异表达基因及其相关通路与过敏体质的关系,从基因水平探讨过敏体质成因、特征及其发病机制。结果中医古代文献尚未形成对过敏体质的系统论述,中医体质学明确提出过敏体质的概念并对过敏体质防治有突破性认识。中医体质学认为对过敏体质者调治的重点应该是针对“过敏人”,而不是一味避开“过敏原”,对于具有过敏体质而未发病的人群,积极改善其过敏体质,可实现病因预防。基因表达谱研究发现,过敏体质者与平和体质者相比,外周血基因表达谱上调的基因有86个,下调的基因有111个。其中FOS基因、IL-16基因表达的上调与近期对其与过敏的相关研究结果相一致;而其他表达差异的基因中,涉及的生物信息学通路与过敏关系密切的有IL-4signaling pathway及p38MAPK signaling pathway等,差异表达基因在上述生物信息学通路中起重要作用,可能在过敏体质发生过敏性疾病的过程中起重要调节作用。结论基于中医体质学理论的过敏体质调治思想,对于阻止过敏体质相关过敏性疾病的发生、发展,具有重要的指导意义;过敏体质者与平和体质者相比FOS基因、IL-16基因表达的差异是其基因水平的重要表现;其他表达差异参与IL-4signaling pathway及p38 MAPK signal ing pathway的调节过程,与过敏体质发生过敏性疾病有密切关系。更多还原

【Abstract】 Objective:Analysis the ancient and modern recognition by Sorting pertinent literature,Supplement and consummate the theory system of the Allergic constitution;Study the peripheral blood gene expression profile of the Allergic constitution by gene chip technique.Not only providing theory and experiment support for identifying the Allergic constitution but also for the prevention and treatment of hypersensitivity disease.Methods:Analysis the ancient and modern recognition by Sorting pertinent literature,Discuss concept,source,characteristic,diagnosis,intervention of The Allergic constitution deeply.Supplement and consummate the theory system of the Allergic constitution;15 cases of the Allergic constitution and 30 cases of the Balanced constitution were selected by the standard of the Allergic constitution and the Blanced constitution.The regular physical examination,TCM symptoms and syndromes were investigated accordingly.Total RNA was extracted from peripheral blood,and it was amplified and labeled.The sample were checked by Sentrix(?) Human-6 Expression Bead Chip.The data was analyzed and the gene symbols with significant difference were searched in GENE BANK database.the gene differential expression profiles and correlated pathway were analyzed.Results:"Allergic constitution "has not been found in ancient literature of TCM.The constitutions of TCM bring new ideas to the recognition of the the Allergic constitution.it considered the emphasis of medical care to the Allergic constitution is not the sensitinogen but the human being who suffer from hypersensitivity disease.The results showed that the peripheral blood gene expression levels were different in the Allergic constitution Comparing with the Blanced constitution,There were 86 genes expression up-regulated and 111 genes expression down-regulated.Fos gene and IL-16 gene up-regulated among the total,the result have resemblance with the findings about fos gene and IL-16 gene recently;several gene have intimate relationship with the IL-4signaling pathway and p38 MAPK signalilng pathway,the findings is valuable for the learning of the Allergic constitution to TCM.Conclusions:The sought about prevention and cure to the Allergic constitution based on the theory of The constitutions of TCM.it benefits the prevention and treatment of hypersensitivity disease.The peripheral blood gene differential expression profiles in the Allergic constitution was found for the first time.Fos gene and IL-16 gene up-regulating and several gene having intimate relationship with the IL-4signaling pathway and p38 MAPK signalilng pathway maybe the characteristic of the Allergic constitution,更多还原