环状RNA在原发性高血压发病中的作用机制研究

Essential hypertension (EH) is a common chronic non-communicable disease, whose pathogenesis research has become a hot topic in recent years. Recent studies suggests that circRNA expression may change with the onset and development of the essential hypertension. In the current study we aim to focus on the research hotspot in the pathogenesis of hypertension and eventually screen target circRNA, with the established chronic disease monitoring network , the circRNA chip detection, and biological pathway analysis. A case-control study is applied to verify the association between circRNA and essential hypertension in population. According to the interaction network of circRNA with miRNA and GO level network, the target circRNA and the corresponding miRNA interaction analysis is conducted. In addition, we will comprehensively analysze the main effect and interaction between circRNA and environmental factors. Finally, we will develop the hypothesis regarding the regulation of gene expression of circRNA in the development of essential hypertension. Target circRNA, to serve as clinical diagnostic markers and therapeutic target of essential hypertension, will provide scientific basis for screening patients with essential hypertension,choosing drugs ,and provide reference for the study of other complex diseases.

原发性高血压是一种常见的慢性非传染性疾病，针对其发病机制的研究已成为近年来国内外学者探讨的热点。近年研究提示circRNA表达谱的改变可能与高血压的发生、发展有关。本研究从高血压发病机制的研究热点切入，利用已建立的慢性病监测网络，通过circRNA芯片检测，结合生物学通路分析筛选目标circRNA。采用病例对照研究，对目标circRNA的表达进行人群验证。根据circRNA与miRNA的互作网络和GO功能层次网络，对目标circRNA与对应的mRNA进行互作分析，综合分析circRNA主效应及与环境因素的交互作用，建立circRNA调控基因表达在原发性高血压发病过程中的分子机制假说。以目标circRNA作为原发性高血压临床诊断标志物或治疗靶点，将为原发性高血压易感者的筛选和药物选择提供科学依据，也为其他复杂性疾病的研究提供参考。

原发性高血压（Essential hypertension，EH）是一种机制复杂的多因素慢性非传染病，已经成为严重威胁人类身体健康的重要公共卫生问题。本研究运用芯片技术高通量检测并筛选原发性高血压相关的circRNA，通过病例对照的方法结合生物信息学的预测和分析，在人群中验证目标circRNA在原发性高血压发病的作用。.根据前期环状RNA表达谱芯片检测的荧光信号的强度，比对环状RNA的表达水平进行聚类分析，利用miRanda软件对差异化表达的环状RNA进行靶向miRNA预测，确定差异化显著且可预测靶向miRNA的目标circRNA，通过病例对照研究进行人群验证。. 血管内皮损伤相关circRNA与原发性高血压的关联性研究：通过实时荧光定量PCR技术测定circRNA（hsa_circ_0014243、hsa_circ_0126991和hsa_circ_0041000）和靶向预测的miRNA（hsa_miR-10-5p和hsa_miR-497-5p）的相对表达量，结果显示：血管内皮损伤相关的hsa_circ_0014243和hsa_circ_0126991在人体内低表达是原发性高血压发病的保护因素；与hsa_circ_0014243和hsa_circ_0126991相互作用的hsa_miR-10a-5p在人体内低表达是原发性高血压发病的危险因素；在60周岁以上的人群中，hsa_circ_0014243和hsa_circ_0126991二者低表达的保护效应更强，提示随之年龄的增长，circRNA表达谱的变化与疾病发生发展之间的关系更加紧密；在hsa_miR-10a-5p ∆Ct值 ≤ 3.2时，hsa_circ_0126991低表达的保护效应也得到增强，提示随着hsa_miR-10a-5p表达水平的增加能够促进hsa_circ_0126991低表达的保护作用；hsa_circ_0014243和hsa_circ_0126991在原发性高血压中具有一定的诊断价值，同时联合与之对应的miRNA能够提高它们的联合诊断价值。.炎症因子相关circRNAs与原发性高血压的关联性研究：通过实时荧光定量PCR技术测定circRNA（hsa_circ_0037911和Hsa_circ_0002161）和靶向预测的miRNA（hsa-miR-637）的相对表达量，结果显示：炎症相关的h