中药对“正虚”“瘀毒”证型骨髓增生异常综合征组蛋白乙酰化机制差异性表达的干预研究

组蛋白修饰作为公认的细胞分化命运控制机制与MDS骨髓细胞分化障碍特点高度吻合。“组蛋白乙酰化-转录因子-转录基因表达-细胞凋亡”机制研究成为MDS表观遗传学研究方向之一。课题组结合既往MDS中医药临床研究、中医证型与其骨髓细胞双向凋亡机制研究、MDS组蛋白乙酰化修饰作用研究等前期工作，采用MDS骨髓细胞体外培养、免疫沉淀技术（IP）、Realtime-PCR、westernblot等实验方法，拟解决以下几个科学问题： 1.阐释HDACs/GATA1/TLR2相关信号通路介导的MDS表观遗传学机制；2.分析不同“正虚”、“瘀毒”中医证型MDS组蛋白乙酰化的特征，证实“MDS不同中医证型的‘组蛋白乙酰化-转录-基因表达-细胞凋亡’机制的表达差异性”假说；3.证实有效扶正中药核心组方对低危型MDS相关信号通路的调控作用，进一步阐明其疗效的内在机理，为中医药有效治疗MDS提供新的理论依据。

It is widely known that histone modification is the control mechanism of the fate of cell differentiation, highly according with the pathological features of Myelodysplastic syndrome(MDS)cells differentiation disorders. “Histone acetylation – transcription factor - transcriptional gene expression- apoptosis "mechanism research has become one of the research directions of MDS epigenetics. Based on the previous MDS clinical studies of traditional Chinese medicine (TCM), TCM syndrome type and the bidirectional apoptosis mechanism of bone marrow cells of MDS、histone acetylation modification function studies and so on . We will use MDS bone marrow cells cultured in vitro, immunoprecipitation (IP), Realtime-PCR, Western blot and other experimental methods that intend to further solve the following some scientific problems:1. Inerpret HDACs/TLR2/GATA1histone acetylation involving in signaling pathways mediates epigenetic mechanism of MDS;2.Analyze the histone acetylation features of different TCM syndromes of “Vital Qi Deficiency and Stasis Toxin” ,and confirm differential of expression. ”histoneacetylation – transcriptionfactor - transcriptional gene expression - apoptosis ”mechanism " hypothesis;3. Confirm composition of core in Chinese herbal medicine about effective support vital qi which will effect on the low risk MDS related signal pathway, further clarify inherent efficacy mechanism ,and provide a new theoretical basis for the Chinese medicine is effective in the treatment of MDS.