lncRNA H19在细颗粒物（PM2.5）致心力衰竭发生发展的作用研究

There is considerable evidence that fog and haze pollution increases the risk of cardiovascular disease. Ambient fine particulate matter (PM2.5) that endangered human health are the main pollutants for fog and haze formation. Long-chain non-coding RNA (lncRNA) plays an important regulatory role in the pathogenesis of environmental chemicals. Our previous study shows that PM2.5 exposure significantly increased the onset of heart failure and cardiac sudden death.Pre-experiment further indicated that the expression level of lncRNA H19 significantly increased in patients with heart failure in winter, it was also elevated in PM2.5-induced cardiomyocytes and significantly correlated with Wnt signaling pathway. However the mechanism of H19 in PM2.5 induced heart failure is unclear. In present study, PM2.5 will be selected to induce heart failure in mice/rat and myocardiac cell. By establishing overexpression and knockdown systems respectively, we will use RNA-Seq, qPCR, immunoblotting, co-immunoprecipitation and other methods to analyze the changes in myocardial remodeling, inflammation, apoptosis, energy metabolism. We attempt to elucidate the mechanism of H19 in PM2.5-induced heart failure from clinical, animal, cellular, molecular and gene levels, initiate a new idea for the mechanism of PM2.5-induced heart failure, and provide new evaluation indicators and intervention targets for the prevention and treatment of PM2.5-induced heart failure.

大量证据表明雾霾污染增加心血管疾病的风险，PM2.5是雾霾污染中对人类健康影响最主要的成分。长链非编码RNA（lncRNA）在环境化学物致病中具有重要的调控作用。我们前期研究成果表明PM2.5 暴露显著增加心力衰竭的发作甚至猝死的发生，预实验进一步提示lncRNA H19在冬季心衰患者中的表达显著上升，在PM2.5诱导的心衰细胞中表达同样升高，且与Wnt信号途径明显相关，然而H19在PM2.5促心力衰竭中的作用机制尚不清楚。本研究以PM2.5 为诱导物，构建心衰动物模型及细胞模型，通过建立过表达和敲低体系，采用 RNA-Seq、qPCR、免疫印迹、免疫共沉淀等方法，分析心肌重构、炎症、凋亡、能量代谢等变化，从临床、动物、细胞、分子、基因等多层次，阐明H19在PM2.5促心力衰竭中的作用机制，为PM2.5 致心衰机制的研究开辟一种新的思路，为防治PM2.5促发心衰提供新的评估指标与干预靶点。

大量证据表明雾霾污染增加心血管疾病的风险，PM2.5是雾霾污染中对人类健康影响最主要的成分。长链非编码RNA（lncRNA）在环境化学物致病中具有重要的调控作用。本课题构建了阐明 H19 在 PM2.5 诱导的心衰中功能及其分子机制，为 PM2.5 致心衰机制的研究开辟一种新的思路。我们研究成果表明PM2.5 暴露lncRNA H19在冬季心衰患者中的表达显著上升，在PM2.5诱导的心衰细胞中表达同样升高，且能靶向调节Wnt信号通路。本研究以PM2.5 为诱导物，构建心衰动物模型及细胞模型，通过建立过表达和敲低体系，采用 RNA-Seq、qPCR、免疫印迹、免疫共沉淀等方法，分析心肌重构、炎症、凋亡、能量代谢等变化，从临床、动物、细胞、分子、基因等多层次，阐明H19在PM2.5促心力衰竭中的作用机制。