NADPH oxidase/ROS/NF-κB信号通路在飞燕草素抑制单核-内皮粘附中的作用机制研究

来源 :2012第二届中韩植物化学物国际学术研讨会 | 被引量 : 0次 | 上传用户:chcer1988
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  Objective Cadiovascular dieases induced by atherosclerosis has been demonstrated to be the leading cause of death in the western countries,and monocyte adhesion to the vascular endothelium and their subsequent trans-endothelial migration are the pivotal early events in atherosclerosis.In present study,we tried to identify the effect of Delphinidin,belonging to the group of anthocyanin,on adhesion of monocytes to endothelial cells induced by ox-LDL.Method:Monocyte adhesion to endothelial cells was measured using fluorescently labeled monocytic THP-1 cells,and the migration assays were performed by CCK-8.The intracellular radical scavenging activity of Delphinidin was investigated by detecting intracellular ROS level labelled by DCFH-DA.The cellular levels of P-selectin and ICAM-1 were detected by ELISA and western blotting analysis.Additionally,the role of ROS/p38MAPK/NF-κB signaling pathway in the inhibition of endothelial dysfunction by Delphinidin was determined by qRT-pcr,western blotting analysis and dual luciferase reporter gone assays.Result:The results showed that pretreatment with Delphinidin (50,100,or 200μM) dose-dependently decreased ox-LDL-induced up-regulation of the expression of ICAM-1 and P-selectin,and the enhanced adhesion and transmigration of monocytes.To determine the role ofNADPH oxidase/ROS/NF-κB pathway,NADPH oxidase subunit (Nox2 and p22phox) mRNA expression,intracellular ROS level,Iκ B-α degradation,NF-κB transcription activity and protein expression were measured.The results showed that Delphinidin attenuated ox-LDL-induced NADPH oxidase subunit (Nox2 and p22phox) mRNA expression,generation of ROS,IκB-α degradation,NF-κB transcription activity and protein expression in endothelial cells in a dose-dependent manner.Conclusion:These results .suggest that Delphinidin attenuates ox-LDL induced expression of adhesion molecules (P-selectin and ICAM-1)and the adhesion of monocytes to endothelial cells by inhibiting NADPH oxidase/ROS/NF-κB pathway.These findings provide a basis for the design of potent antiatheroscterotic agents that will have therapeutic potential in the prevention of AS.
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