microRNA在高原性肺动脉高压形成过程中的作用机制研究

项目名称： microRNA在高原性肺动脉高压形成过程中的作用机制研究

项目编号： No.81460012

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 白玛康卓

作者单位： 西藏大学

项目金额： 50万元

中文摘要： 高原性肺动脉高压(HAPH)是低氧性肺动脉高压的一种，至今发病机理尚不清楚，难治难防，病程不可逆。本项目拟在不同海拔世居藏族和移居汉族HAPH患病率调查的基础上通过提取血液样本总RNA采用miRNA芯片技术对不同海拔藏族、汉族人群HAPH患者与健康人群miRNA表达谱差异分析；通过实时定量PCR技术对miRNA结果的可靠性进行验证，从而筛选得到与高原性肺动脉高压相关micro RNA(miRNA)的靶基因；在高原自然环境下（海拔3680m）建立高原性肺动脉高压大鼠模型，观察HIF-VEGF-Notch信号通路中各相关因子表达变化。旨在从表观遗传学角度发现HAPH新的无创性诊断标志物，并探讨HIF-VEGF-Notch信号通路在肺血管重构中的作用，为预防和治疗HAPH提供新的靶点。

中文关键词： 肺动脉高压；低氧性肺动脉高压；肺血管重塑；信号通路

英文摘要： High Altitude Pulmonary Hypertension (abbreviation as HAPH) is a typical case of hypoxia pulmonary hypertension and its mechnaism is unclear so far. Moreover, there is no effective therapeutic method to prevent or cure this disease. Our project, with methods: 1) through miRNA chip to analyse the gene differential expression between Tibetan people and Han people living at different altitudes based on the investigation of racial variation in the prevalence of HAPH. 2) to testify chip results with real time PCR method. 3）to predict the candidate genes which contribute to the incidence of HAPH disease based on the gene predictive software. 4) to construct the HAPH mice model（with a 3680m-altitude environment） to obeserve the change of gene expression of HIF-VEGF-Notch signaling pathway, in order to testify our hypothesis. Based on those results and epigenetic knowlege, we may discover new biomarkers for the diagnosis of HAPH and have a futher understanding of the function HIF-VEGF-Notch signaling pathway on remodeling of blood vessle in lung tissue, more importantly, we wish we could find a promising gene target for the prevention and cure of HAPH disease.

英文关键词： pulmonary hypertension;hypxic pulmonary hypertension;pulmonary vascular reconstruction;Signaling pathway