大气细颗粒物暴露引起糖代谢异常的分子机制研究进展

Advances on mechanisms of abnormal glucose metabolism induced by ambient fine particulate matters

近年来,空气污染对人体健康的危害日益受到众多研究学者的密切关注。大气细颗粒物(fine particulate matter,PM2.5)是指空气动力学直径小于或等于2.5μm的颗粒物,这些颗粒物由于粒径小,可被吸入下呼吸道甚至进入肺泡,进而引发众多不良健康效应。大量的流行病学研究表明PM2.5暴露是糖尿病的高危因素。糖尿病是一类在遗传因素和环境因素相互作用下,以胰岛素抵抗或胰岛素分泌不足为主要特征的慢性代谢性疾病,我国的糖尿病患病率已经从1990年的3.3%上升到2016年的6.6%,目前患者人数居世界首位,形势十分严峻。基于大气PM2.5引发糖代谢异常的生物学机制尚未清楚,本综述对近几年大气细颗粒物导致糖代谢异常的发生发展分子机制进行总结,包括炎症反应、氧化应激、内质网应激、核因子-κB(NF-κB)信号通路的激活等机制,还对肠道微生物相关的机制,特别是微生物代谢产物短链脂肪酸、胆汁酸代谢、内毒素代谢和肠黏膜通透性的改变等作用通路在糖代谢过程中的介导作用,进行详细的论述,希望能为PM2.5暴露所引发的糖代谢异常的新干预方法及措施的提出与建立提供科学依据。

Recently, the adverse health effects of air pollution have become increasingly concerned. Ambient fine particulate matters(with aerodynamic diameter ≤2.5 μm, PM2.5) can deposit in the lower airway, and even enter the pulmonary alveoli, causing multiple adverse health effects. A large number of epidemiological studies have indicated that ambient PM2.5 exposure is a crucial risk factor for diabetes. Diabetes is a chronic metabolic disease characterized by insulin resistance and/or insufficient insulin secretion under genetic and environmental interactions. The morbidity of diabetes in China has increased dramatically from 3.3% in 1990 to 6.6% in 2016, and the situation is serious with diabetes patients ranking the first place in the world. Since the underlying biological mechanisms are not fully elucidated, this review summarized recent research on the potential mechanisms of ambient PM2.5-induced abnormal glucose metabolism. In addition to inflammation reaction, oxidative stress, endoplasmic reticulum stress, and activation of nuclear factor κB(NF-κB) signaling pathway, gut microbiota-related pathways, especially the mediation roles of microbial metabolic products such as short chain fatty acids, bile acid metabolism, endotoxin metabolism, and change of intestinal permeability were also discussed in detail, aiming to provide scientific evidence for the propose and establishment of novel intervention methods and measures against abnormal glucose metabolism induced by PM2.5.