Biochanin A Alleviates Lung Damage Injured By PM_2.5

Haze pollution has been emerging a global environmental problem,influencing air quality,climates,economy and human health.Notably,PM_2.5（particulate matter with an aerodynamic diameter less than 2.5 micrometers）significantly accounts for a variety of adverse health effects,especially pulmonary diseases such as severe lung cancer.We established a rat model of nonsurgical intratracheal instillation and employed Isobaric Tags for Relative and Absolute Quantitation（iTRAQ）coupled with LC-MS/MS to analyze differentially expressed proteins（DEPs）.We discovered 163DEPs in response to intratracheal instillation of PM_2.5,including 83 up-regulated proteins and 80 down-regulated proteins and identified six remarkable DEPs as biomarkers,including HMOX1,MP2K5,XRCC1,E9PTZ7,A1AG and KNT2.Moreover,we exerted western blot in AEC-II cells exposed to PM_2.5 to validate biomarkers,suggesting that these three proteins,MP2K5,HMOX1,A1AG can be regarded as biomarkers for lung damage injured by PM_2.5.GO and STRING program suggest that oxidative stress stimulus,inflammatory response and immune regulation were the key processes of lung damage.KEGG analysis revealed that calcium signaling,MAPK and PI3K/AKT were specifically responsible for lung damage.Protein Tnnc1,MP2K5 and PkB kinase were involved in calcium signaling,MAPK signaling and PI3K/AKT pathway,respectively,providing implications for preventive and therapeutic strategies of PM_2.5 associated pulmonary diseases.At the same time,we investigated the protective effects of biochanin A（BCA）,BCA,a kind of plant-derived isoflavone.Histopathology indicated that lung structures,such as bronchioles,alveolus,and pulmonary vessel had normal appearances in control and most severe damage in the PM_2.5-H exposure group,while lungs damage was strongly alleviated with the increase of BCA supplement.Moreover,PM_2.5exposure increased oxidative stress and inflammatory response.In specific,PM_2.5significantly decreased activity of antioxidase,such as SOD,CAT and GSH-P_X while obviously increased the level of oxidative stress such as MDA,LDH,AKP and inflammatory response such as ALB,TNF-α,IL-2,IL-8 compared with the control group（p<0.05）.On the contrary,BCA increased the activity of antioxidase,and decreased oxidative stress and inflammatory response with a dose-dependent manner（p<0.05）,which indicating that BCA can alleviate lung damage through mediating oxidative stress and inflammatory response.Thus,BCA can be used as a candidate of chemotherapeutic agents to alleviate lung damage,and decrease the incidence of lung cancer.We envision that our study will provide new diagnostic,preventive and therapeutic strategies for PM_2.5 correlated lung diseases.It will provide the theoretical basis about intervention and control of food nutrients on PM_2.5-induced lung damage...