基于自噬途径研究大气细颗粒物PM2.5诱导的神经缺血性损伤

Epidemiological studies showed that air pollution caused deaths in the indoor and outdoor, the rate of stroke reached 34% and 40%, respectively. Relevant results suggested that people lived in particulate matter; especially PM2.5 pollution serious areas had a significantly higher incidence of ischemic stroke. After entered into the body, particulate matter induced oxidative stress and produced ROS. As a kind of signaling molecules, ROS involved in cell autophagy activation. In the nervous system, moderate autophagy can remove redundant metabolic protein, but insufficient or excess autophagy may lead to neuronal cell death. However, the exact role of PM2.5 induced autophagy via ROS remained unclear in cerebral ischemia damage. The project intended to collected fine particles PM2.5 from north China city-shanxi, researched neurological ischemic injury induced by PM2.5 through autophagy pathway in terms of animal studies, which will help set up biomarkers for test and risk evaluation, and open up therapeutic approaches for treating, ameliorating, or preventing related injuries resulting from PM2.5 exposure in atmospheric polluting environment.

流行病学研究表明，室内、外空气污染造成的死亡中，脑卒中分别达到34%和40%。特别是有相关结果提示，在大气颗粒物，尤其是PM2.5污染比较严重的地区，其人群缺血性中风的发病率显著增高。颗粒物进入体内后引发的机体氧化应激产生的ROS作为一种信号分子参与细胞的自噬激活。在神经系统中，适度的自噬可以清除多余的代谢蛋白，而自噬不足或过强会导致神经细胞死亡。然而，PM2.5通过ROS诱发的自噬在脑缺血缺氧损害中的确切作用尚存不清楚。本项目拟采集我国北方城市——山西大气细颗粒物PM2.5，在整体动物水平研究PM2.5通过自噬途径诱导的神经缺血性损伤，建立对该效应检测的生物标记，为污染地区相关疾病的预防、早期诊断提供一定的实验依据。

本项目以PM2.5长期低浓度接触和污染事件所引发的健康危害，特别是流行病学调查显示的PM2.5与缺血性脑中风发病率增高的相关性为研究背景，通过实验建立整体动物染毒模型、小鼠缺血性中风MCAO模型、自噬激活/抑制模型，探讨PM2.5能否通过自噬途径诱导神经缺血性损伤效应。实验结果表明：PM2.5暴露可能通过激活自噬过度表达，诱导内皮功能障碍，促进细胞凋亡，从而恶化缺血性中风的发生发展。由此提示可能的作用途径：PM2.5暴露激活ROS表达，上调Beclin 1和LC3-II水平，增加HIF-1α、ET-1表达，引发神经细胞凋亡。该研究成果揭示了自噬行为在PM2.5诱导神经缺血性损伤过程中发挥的作用，建立对该效应检测的生物标记，为PM2.5暴露安全评价、排放标准修订以及污染地区相关疾病的预防、早期诊断提供一定的实验依据。