Liraglutide prevents high glucose-induced adhesion of endothelial cells to monocyte by targeting IKK/NF-κB / 中国医师杂志

ABSTRACT

Objective To investigate the inhibition effect of liraglutide (lira) on high glucose-induced adhesion of endothelial cells to monocyte.Methods Human umbilical vascular endothelial cells (HUVECs) induced by high glucose (20 mmol/L) were incubated with different concentrations of liraglutide (0,0.3,3,30 nmol/L) for different time.THP-1 cells were pre-labeled with Calcein-AM and then incubated with HUVECs for 1 h,M199 medium were used for washing the nonadherent cells for 3 times,and the adhesion of HUVECs to THP-1 cells were measured by Fluorence microplate reader;real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) were employed to detect the mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1),respectively.Western blot was used to measure the content of IκBα,p-IκBα and the distribution of p65 in plasma and nuclear.GST-IκBα was introduced as substrate to test the activity of IκB-kinase (IKK).Results The adhesion of HUVECs to THP-1 (P ＜ 0.01),the mRNA and protein expression of VCAM-1 and ICAM-1 (P ＜ 0.05,P ＜ 0.01),the phosphorylation of κBα (P ＜ 0.05,P ＜ 0.01),the translocation of p65 subunit from plasma to nuclear and the activity of IKK (P ＜ 0.01) in HUVECs were all elevated by stimulation with 20 mmol/L glucose,and the content of IκBα was decreased accordingly (P ＜0.01).Pre-incubation with lira could reverse the above effect of high concentration of glucose.Conclusions Lira could reduce VCAM-1 and ICAM-1 expression through IKK/NF-κB pathways in 20 mmol/L glucose-induced HUVECs,which finally suppress THP-1-HUVECs adhesion.