中文摘要
基于DNA甲基化/羟甲基化的表观遗传学在阐明疾病基因和环境相互作用方面发挥重要作用,但早发冠心病及血瘀证发生发展的机理及中药干预机理尚未全面阐释。因此,我们在前期早发冠心病血瘀证遗传基因及甲基化研究的基础上,拟通过采用高通量寡核苷酸芯片筛选、甲基化特异PCR、羟甲基化DNA免疫共沉淀法、iTRAQ差异蛋白质组学质谱定量及生物信息分析等技术,开展①探讨DNA甲基化/羟甲基化修饰与早发冠心病血瘀证患者发生发展的相关机制;②养心通脉方干预细胞的DNA甲基化/羟甲基化修饰;③血府逐瘀汤对早发冠心病血瘀证患者和家系进行辨证调理,以方验证和构建早发冠心病血瘀证的甲基化/羟甲基化修饰的调控网络。从基因甲基化/羟甲基化-内部表型-疾病模式-中药干预的系统生物学角度把握早发冠心病血瘀证的基因表达与临床应用的结合点,以期发现中药在冠心病血瘀证表观遗传层面的调控机制,以促进冠心病中医药预防和临床治疗。
英文摘要
Geneticist based on DNA methylation/methylolation play an important role in elucidating disease gene and environment interaction.But the mechanism of premature coronary heart disease with blood stasis syndrome has not been given a comprehensive interpretation. In the basis of previous research on genetic genes of blood stasis syndrome in premature coronary heart disease , We 'll do the experiment by detection the whole genic DNA methylation profile through the high- throughput filtration technologies on oligonucleotide microarray , biological information analysis, Methylation-specific polymerase chain reaction, hMeDIP, two-dimension gel electrophoresis and mass spectrum for①To investigate the mechanism of DNA methylation/methylolation and the development of the blood stasis syndrome in patients with premature coronary heart disease ②Yangxin Tongmai Fang`s intervention in the DNA methylation/methylolation in the level of animal and cell and the analysis and discussion of traditional Chinese medicine intervention on the model of DNA methylation/methylolation in epigenetic regulation mechanism.③Though the use of xuefu zhuyu decoction on blood stasis syndrome of premature coronary heart disease patients and pedigree with syndrome differentiation treatment, the connection between research of gene epigenetics and clinical application will be comprehended from the view of systems biology include gene methylation/methylolation - internal phenotype - patterns of disease - Chinese medicine intervention. The above research wil discover the mechanism of Chinese medicine intervention in regulating the methylation of premature coronary heart disease and pedigree with blood stasis , which provide a new idea to promote Chinese medicine prevention and therapy of coronary heart disease with blood stasis syndrome.
