定喘汤宣降清三法干预合胞病毒感染T-bet哮喘易感基因及代谢组学研究

项目名称： 定喘汤宣降清三法干预合胞病毒感染T-bet哮喘易感基因及代谢组学研究

项目编号： No.81473726

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 崔振泽

作者单位： 大连医科大学

项目金额： 76万元

中文摘要： 呼吸道合胞病毒（RSV）感染可导致毛细支气管炎(肺炎)、诱发哮喘。项目前期研究初步探讨定喘汤干预RSV肺炎药效物质基础，发现该病机证候群的生物学基础，但该结果是否适用于异病同治还有待于深入研究与验证。本研究提出定喘汤宣升与清降并用改善RSV感染的免疫损伤，发散与收敛兼施调节Th1/Th2的免疫失衡的假说。针对基本证型变化，动态采集受试者证候、代谢组学和疾病信息，通过个体评价、群体分析，代谢网络构建相关分析研究证候代谢组学之间的动态关联。探求该证在三种疾病中的共性标志物、代谢网络及哮喘易感基因位点的表达。力图通过临床和实验研究，明确RSV感染前后T-bet基因单核苷酸多态性的变化及Th1/Th2免疫失衡状态。继而用定喘汤干预RSV模型鼠，考察RSV鼠体内整体代谢网络的变化，并结合临床试验结果，探讨符合中医症候群的生物标记物群,进一步阐明中医整体宏观辨证与生物组学微观辨病的重要性。

中文关键词： 中医药治疗；代谢组学；呼吸道合胞病毒；哮喘；基因多态性

英文摘要： Respiratory syncytial virus (RSV) is the common cause of pneumonia, bronchiolitis and inducing asthma. In our primary research we discussed that Dingchuantang decoction can intervene the therapeutical basis of RSV pneumonia and we also found out the biological basis of symptoms in RSV pneumonia. Whether this result apply to treating same disease with different methods has yet to be further study and validation. These observations have led us to posit that Dingchuantang decoction can improve immune injury of RSV infection and regulate the imbalance of Th1/Th2. Using randomized controlled trial, we collected the information of symptoms, metabonomics and disease to establish of the dynamic association of symptoms and metabonomics by individual evaluation, population analysis and metabolic network. We explored that the relationship between common metabolic biomarkers in the three diseases and single nucleotide polymorphism of T-bet gene which is genetic susceptibility to asthma. Combination of variation of metabolic network and clinic research, we discussed the biomarker which is accordance with the symptoms of traditional Chinese medicine. Further more, we clarified the important value of the aspect of macroscopic syndrome differentiation of traditional Chinese medical entireties and microcosmic diagnosis differentiation of metabolomics after ingesting Dingchuandang decoction to RSV rat model. Combining the above researching, we provided a scientific basis of using traditional Chinese medicine to prevention of RSV infection and the subsequent development of asthma later in clinical practice.

英文关键词： Traditional Chinese medicine treatment;metabonomics;Respiratory syncytial virus;asthma;Gene polymorphism