基于动态生物网络的慢性乙型肝炎典型证候病证关系分子机制研究

项目名称： 基于动态生物网络的慢性乙型肝炎典型证候病证关系分子机制研究

项目编号： No.81473443

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： 陈启龙

作者单位： 上海中医药大学

项目金额： 75万元

中文摘要： 中医辨证治疗慢性乙型肝炎(CHB)有独特作用，但CHB病证分子机制尚未阐明。近年来生物网络技术为CHB研究提供了新方法。我们前期研究发现：CHB不同证候miRNA表达差异明显，分子网络显示虚证和虚实夹杂较实证预后更差；蛋白表达谱显示CHB证候间有明显分离趋势。据此我们推测：不同证对应的CHB病可能产生不同预后，其对应的病证机制也不同。本课题拟在此基础上，以临床常见且具有代表的CHB典型实证（肝胆湿热证）、虚实夹杂（肝郁脾虚证）、虚证（肝肾阴虚证）为切入点，以疾病中隐证型（无证可辨）和健康者为对照，检测其miRNA/mRNA/protein表达谱信息，设计中医药特色算法，构建CHB典型证候相关动态分子网络，采用生物信息学方法筛选潜在分子标志物，并运用qPCR/Western Blot 验证与CHB典型证候的关系。本课题将有助于揭示CHB病证分子机制，为慢性乙型肝炎中医治疗提供新线索。

中文关键词： 慢性乙型肝炎；中医证候；病证结合；生物网络

英文摘要： Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for Chronic Hepatitis B (CHB), which requires a traditional diagnose method to differentiate the TCM syndrome. However, the Disease-Syndrome Mechanism of CHB still is inexplicit. Molecular biological network was used for many chronic disease studies, which exhibits a new route for CHB research. In previous studies, we found that the miRNA expression levels are great differences among the TCM syndromes of CHB. The miRNA-target dynamical network suggested that the prognosis of Excessive-deficient syndrome and Deficient syndrome might poorer than Excessive syndrome in CHB patients. The expression profile of serum protein also implicated that the CHB syndromes have distinct separation tendency. Based on these findings, we hypothesized the relationship between Disease and Syndrome of CHB is complex, the different Syndrome might causes different Disease in prognosis, and the related molecular mechanism of Disease-Syndrome also different. In the present project, the representative and common clinical Excessive syndrome (Liver-gallbladder dampness heat syndrome, LGDHS),Liver depression and spleen deficiency syndrome (LDSDS), and Deficient syndrome (Liver-Kidney Yin Deficiency Syndrome, LKYDS) of CHB patients were studied, the Occult syndrome (Differentiation of Syndrome Unavailable, DSU) and healthy donors act as control. We first deteced the miRNA, mRNA, and protein expression profiles from CHB samples. Then, the dynamical molecular networks of CHB syndromes were constructed using TCM special biological algorithm. Furthermore, the potential molecular biomarkers of CHB syndromes were screened by bioinformatics, and explore the correlation between the biomarkers and CHB syndromes based on qPCR/Western Blot validation. The project would help uncover the molecular mechanism of Disease and Syndrome of CHB, and provide clues to TCM treatment of CHB patients.

英文关键词： Chronic Hepatitis B (CHB);Traditional Chinese medicine (TCM) syndrome;Disease and Syndrome;Biological network