复方青黄散对骨髓增生异常综合征患者线粒体DNA拷贝数变异的影响及分子机理的研究

项目名称： 复方青黄散对骨髓增生异常综合征患者线粒体DNA拷贝数变异的影响及分子机理的研究

项目编号： No.81503429

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 杨秀鹏

作者单位： 中国中医科学院西苑医院

项目金额： 18万元

中文摘要： 前期研究表明，含砷中药青黄散治疗骨髓增生异常综合征（myelodysplastic syndromes,MDS）疗效优于国外最新药物, 尤其是对染色体核型正常的患者，其有效率明显高于其他异常核型。对于作用机理的研究显示，青黄散对MDS患者有去甲基化作用，体外实验表明一定剂量的砷可引起氧化应激。线粒体是砷体内代谢过程中最敏感的细胞器，最近有研究者报道，MDS患者存在线粒体DNA(mitochondrial DNA，mtDNA)拷贝数变异，且多出现在染色体核型正常的患者。本研究以改良后的复方青黄散为给药手段，通过检测治疗前后MDS患者mtDNA拷贝数变异，验证治疗的作用靶点之一是mtDNA；同时评价mtDNA拷贝数变异与染色体核型之间的关系；还将进一步阐明青黄散作用于mtDNA的作用机理为氧化应激和去甲基化。

中文关键词： 骨髓增生异常综合征；复方青黄散；线粒体DNA；拷贝数变异

英文摘要： Previous research shown that curative effect of traditional Chinese medicine Qinghuang powder was even better than the latest drugs in treatment of myelodysplastic syndrome. Qinghuang powder was more effective in patients with normal karyotype than in other abnormal karyotype. Some studies about mechanism showed that, Qinghuang powder result in a significant genome-wide demethylation. In our vitro study, we found that a certain dose of arsenic can cause oxidative stress. In our body, mitochondria are the most sensitive organelles for arsenic metabolism process. Recently, some researchers found that MDS patients have DNA copy number variation in mitochondrial, and more in normal chromosome karyotype patients. This study will detection MDS mitochondrial DNA copy number variation before and after treatment with new Qinghuang powder, validation one the target of Qinghuang powder in treatment of MDS was mitochondrial DNA, evaluation the relationship between mtDNA copy number variation and chromosome karyotype in MDS patients, and clarify that oxidative stress and demethylation are the role in the mechanism of Qinghuang powder adjusting the mitochondrial DNA copy number variation.

英文关键词： Myelodysplastic Syndromes;Compound Qinghuang Power;Mitochondrial DNA;Copy Number Variation