流行病学研究表明，大气细颗粒物（PM 2.5）诱导的细胞毒性是导致人体呼吸系统和心血管疾病的重要原因。食品中天然抗氧化剂可能通过多通路、多靶点协同机制对PM 2.5诱导的细胞损伤进行调控。本项目以红枣中四种主要天然抗氧化剂Vc、环磷酸腺苷（cAMP）、熊果酸和芦丁为研究对象，采用析因实验设计不同抗氧化剂组合，建立PM 2.5诱导的A549细胞损伤模型；通过体外、细胞模型内抗氧化评价逐步筛选具有最佳协同效果的抗氧化剂组合；进一步研究该组合处理前后细胞内自由基浓度、抗氧化酶（SOD、CAT、LDH、GSH）活性、细胞周期与凋亡、细胞形态等指标的变化，以及细胞损伤主要信号途径（PI3K/Akt、NF-κB、MAPK）上关键基因/蛋白表达的变化，分析与协同效果有关的信号通路，阐明抗氧化剂组合协同调控PM 2.5细胞毒性的分子机制。为预防和治疗由于大气粉尘颗粒引起的呼吸系统和心血管疾病提供理论依据。

The epidemiology study showed that the PM2.5 induced-cell toxicity was one of the main reason of respiratory and cardiovascular diseases. Some natural antioxidants in food may regulate the PM2.5 induced-cell toxicity by multi target and different pathways. In this research, the natural antioxidants (Vc, cAMP, ursolic acid and rutin) in red date were taken as objects. After the design of different combinations antioxidants and establishment of PM 2.5 induced-cell injury model, the antioxidant capacity evaluation was taken in vitro and intracellular in order to select the optimal synergistic antioxidants group. Then effect of the optimal synergistic antioxidants group on the cellular oxidative stress indexes, such as free radicals, antioxidant enzymes activity (SOD, CAT, LDH, GSH), cell cycle and apoptosis were determined. In addition, the key gene and protein expression in PI3K/Akt、NF-κB、MAPK signaling pathways were also evaluated in order to analysis the signaling pathways and molecular mechanisms associated with the synergistic regulation effect. The research findings can provide a theoretical basis to the prevention and treatment of respiratory and cardiovascular diseases induced by atmospheric particles.