中文摘要
冠心病是多基因多因素复杂疾病,血瘀证是其最常见证候。我们研究表明,冠心病血瘀证有特异的miRNA表达谱和miRNA-mRNA调控网络。新近研究发现,miRNA上游存在“竞争性内源RNA”(lncRNA),通过竞争性抑制miRNA与靶基因mRNA 3’UTR的结合,发挥对miRNA和靶基因的调控作用,活血化瘀方药可能是通过改变lncRNA表达水平,恢复其相关miRNA与靶基因之间的失衡状态来治疗冠心病血瘀证。本课题拟选择冠心病血瘀证病例,利用高通量测序、细胞转染、qPCR等技术,筛选与冠心病血瘀证相关的miRNA和lncRNA基因,构建冠心病血瘀证相关lncRNA-miRNA-mRNA调控网络,并通过“以药测证”,观察活血化瘀药物对冠心病血瘀证相关lncRNA-miRNA-mRNA调控网络的影响,阐述冠心病血瘀证病证结合、方证相应理论的科学内涵,为研制治疗冠心病血瘀证的有效方药提供新靶点。
英文摘要
Coronary heart disease (CHD) is a complicated disease with multiple genes and factors involved. Previous researches have shown that CHD Blood Stasis syndrome (BSS) has its unique miRNA expression profile and miRNA-mRNA interaction network. It is newly reported that lncRNA could function as competing endogenous RNA (ceRNA) to inhibit the combination of miRNA and its target mRNA to regulate the miRNA and mRNA. Promoting blood circulation and dissolving blood stasis may treat CHD BSS by balancing the dysregulation of lncRNA and miRNA. In this research we use high-throughput sequencing, bioinformatics, RNAi, qRT-PCR and Western blot to screen out and identify the lncRNA and miRNA and the lncRNA-miRNA-mRNA interaction network correlated with CHD BSS. Then we use promoting blood circulation and dissolving blood stasis medicine to intervene, hoping to elaborate the biological material basis and scientific connotation of medicine-syndrome correspondence from the perspective of epigenetics, and provide new therapeutic targets for developing new medication for CHD BSS.
