Effects Of Combination Of Benzo[a]pyrene And Lipopolysaccharide On The Function Of Huvec And The Underlying Molecular Mechanism

Object: In this study,the effects of benzo[a]pyrene(BaP)combined with lipopolysaccharide(LPS)on the function of cardiovascular endothelial cells and their molecular mechanism were explored to provide scientific data for scientifically evaluating the impacts of atmospheric polycyclic aromatic hydrocarbons(PAHs)and their microbial contamination on the public cardiovascular system.Methods: The human umbilical vein endothelial cells(HUVECs),a model cell of cardiovascular physiology or pathology,were selected as the test cell.Target proteins characterizing endothelial cell function and inflammatory state,such as ET-1,eNOS,TF,PAI-1,IL-6,IL-8,MCP-1,IL-4,IL-10,were selected as biomarkers and detected with enzyme-linked immunosorbent assay and western blot techniques to explore the effects of LPS and BaP on the function and inflammation of cardiovascular endothelial cells.In addition,the key proteins of signal pathways such as AhR,NF-?B,p38,Erk1/2 and JNK were selected as the targets to investigate the molecular mechanism of combined effects of benzo[a]pyrene and lipopolysaccharide.Results:(1)The results of ELISA showed,the expression of IL-6,IL-8 and MCP-1 in HUVEC increased significantly after being exposed to LPS;the expression of IL-6 and MCP-1 decreased after being exposed to BaP;the expression of IL-6,IL-8 and MCP-1 after being exposed to both of LPS and BaP was lower than that of LPS exposed group.And there was no significant change in the expression of IL-4,IL10 and ET-1.(2)The data of western blot showed,the expression of PAI-1 in HUVEC cells increased,the expression of eNOS decreased,and the nucleus Phospho-p38,Phospho-JNK,Phospho-Erk1/2,Phospho-IKK?,Phospho-NF-?B increased after LPS exposure;the expression of eNOS in HUVEC cells increased,the expression of PAI-1 and TF decreased;the nucleus AhR,Phospho-p38,Phospho-Erk1/2 expression increased,Phospho-IKK?,Phospho-NF-?B,Phospho-JNK decreased,after being exposed to both of LPS and BaP,compared with LPS exposed group.Conclusion:(1)LPS could activate IKK-NF-?B signaling pathway through p38,JNK and Erk1/2,promoting inflammatory response of endothelial cells and leading them dysfunction;(2)Low doses of BaP may inhibit the activation of NF-?B through AhR-NF-?B or JNK-IKK?-NF-?B pathway,inhibiting LPS-induced endothelial cell inflammation to some extent,and improving the physiological function of the endothelial cells.