从组蛋白乙酰化调控细胞凋亡角度探讨骨髓增生异常综合征中医“正虚”、“瘀毒”证型特点的表观遗传学机制

项目名称： 从组蛋白乙酰化调控细胞凋亡角度探讨骨髓增生异常综合征中医“正虚”、“瘀毒”证型特点的表观遗传学机制

项目编号： No.81202666

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 陆嘉惠

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 表观遗传学异常是MDS发病的重要病理机制，寻找有效、安全的改变患者表观遗传表达的干预措施是当前临床研究的重要方向。临床已证实"健脾补肾、活血解毒"中药治疗MDS具有良好疗效，为深入探讨其在改善患者表观遗传学方面的靶向作用，阐释异常表观遗传学环节与中医"正虚"、"瘀毒"证型特点的内在联系，证明MDS证型演变的科学内涵和相应的中医治则治法机理，本研究在既往MDS中医"正虚"、"瘀毒"证型演变与西医危度分层、凋亡机制相关性研究的基础上，以"组蛋白乙酰化介导的细胞凋亡通路"为切入点，应用chip-seq技术分析正常人、不同IPSS危度分组MDS全基因组组蛋白H3和H4发生乙酰化修饰的位点及富集程度，分析其与MDS危度分层、恶性程度及转恶趋势相关的动态性变化，观察不同"扶正"、"祛邪"药物构比对此特征性动态变化的差异作用，用以方测证法阐释MDS中医"正虚瘀毒"证型演变理论的表观遗传学机制。

中文关键词： 表观遗传学；骨髓增生异常综合征；组蛋白乙酰化；细胞凋亡；中医证型

英文摘要： Abnormal epigenetics regulation is the important pathogenesis of Myelodysplastic Syndrome(MDS).It is essential to find effective and safe interventions of epigenetics regulation by the current clinical research.In recent years,some clinical studies have confirmed the effect of the Chinese Medicine(TCM) in MDS.In order to further investigate the targeting effect in epigenetics regulation of TCM in MDS,we will clarify the correlation between abnormal epigenetics regulation and TCM syndromes features of Vital Qi Deficiency and Stasis Toxin,which will prove the scientific connotation of TCM syndromes transformation and therapeutic principles.Our previous studies have indicated the Chinese Medicine syndrome of MDS,Vital Qi Deficiency and Stasis Toxin,which is correlated with western medicine risk degrees and dysregulated apoptosis.This time,we will examine acetylation sites and enrichment of genome-wide histone H3 and H4 of the normal and the MDS of different risk degree by chip-seq,which is to analysis the dynamic changes of acetylation,risk degree,and malignancy trend of MDS.Then we will observe the different therapeutic mechanisms with the dynamic changes of the Chinese medicine recipe with different composition of the 'vital-Qi' and the 'eliminating evil' medicine, all that is the TCM syndromes transformation th

英文关键词： epigenetics；MDS；Histone acetylation；cell apoptosis；Chinese Medicine syndrome