大气细颗粒（PM2.5）暴露与心血管疾病的发生密切相关，严重影响人类健康，但确切机理还未明确，造成防治困难。我们最近发现PM2.5急性暴露可以在心肌细胞中激活单磷酸腺苷活化蛋白激酶(AMPK)，并且敲除AMPKα2基因可以促进PM2.5引发的心力衰竭，但AMPK如何影响PM2.5引起的心肌损伤的机制还不清楚。本项目拟通过多功能气溶胶浓缩暴露系统装置对正常和心肌肥厚小鼠进行不同时间的PM2.5暴露处理，结合AMPKα2-/-小鼠和药物激活AMPK的手段，利用PM2.5理化特征分析、心脏病理检测、转录组测序和分子细胞技术，在动物和细胞层面揭示AMPK影响PM2.5引发心血管氧化应激和炎症反应的作用和分子机制，为阐明细颗粒物毒性组分诱发的机体应答与损伤作用机理提供科学依据。

Emerging evidence suggests that long-term exposure to high concentrations of airborne fine particulate matter (PM2.5, aerodynamic diameter<2.5 µm) increases the risk of cardiovascular diseases and induces the adverse health effects in humans. However, we are still far from elucidating the mechanism that induces the adverse effects exerted by PM2.5. We recently found that acute PM2.5 exposure activates AMP-activated protein kinase (AMPK) in cardiomyocytes and PM2.5 exposed AMPKα2-/- mice exhibited cardiac dysfunction. However, how AMPK is involved in PM2.5-induced cardiac injury remains unclear. In this project, control and mice with cardiac hypertrophy will be subjected to PM2.5 exposure using versatile aerosol concentration enrichment system for the indicated interval times. AMPKα2-/- mice and metformin treatment will be used in those PM2.5 exposued experiments. Then, with the analysis of physical and chemical characterizations of PM2.5, cardiac pathological examination, RNA-Sequencing and cell molecular biology techniques, we will reveal the role of AMPK in PM2.5-induced cardiovascula oxidative stress and inflammatory response. Our data may provide novel insights into the mechanism of cytotoxicity and pathogenesis of diseases associated with PM2.5 exposure.