Objective       To study the antagonistic effect of exendin-4 (Ex-4) on human umbilical vein endothelial cells (HUVECs) with endoplasmic reticulum (ER) stress-induced cell apoptosis.       Methods        HUVECs were cultured with RPMI 1640 medium. When the HUVECs grew to around 80% at the bottom of culture flasks

the cells were divided into 4 groups (

n

=8) including: a control group (without any treatment)

an Ex-4 group (Ex-4

8 μg/ml for 45 min)

an endogenous peroxidase blocking solution (EPBS) group (EPBS

100 μL/mL for 30 min)

and an Ex-4+EPBS group [Ex-4 pretreatment (8 μg/mL for 45 min) and EPBS treatment (100 μL/mL for 30 min)

]

. The glucagon-like peptide-1 receptor (GLP-1R) was verified by immunofluorescence method. The cell apoptosis was detected by flow cytometry. The expression of calnexin

C/EBP homologous protein (CHOP) and Bax were detected by Western blotting.       Results      GLP-1R existed in HUVECs. EPBS could significantly increase the apoptosis of HUVECs compared with the control group [(52.27±3.66)% 

vs

(7.25±0.62)%

P

<

0.01)

]

. The rate of cell apoptosis in the Ex-4+EPBS group was significantly lower than that in the EPBS group [(37.77±2.86)% 

vs

(52.27±3.66)%

P

<

0.01)

]

. Compared with the control group

EPBS group could increase the expression of calnexin [(1.76±0.16) 

vs

(1.00±0.05)

P

<

0.01

]

CHOP [(4.58±0.32)

vs

. (1.00±0.12)

P

<

0.01

]

and Bax [(2.25±0.10) 

vs

(1.00±0.06)

P

<

0.01

]

. Compared with the EPBS group

Ex-4 group could significantly reduce the expression of calnexin [(0.42±0.05) 

vs

(1.76±0.16)

P

<

0.01

]

CHOP [(0.64±0.10)

vs

(1.65±0.12)

P

<

0.01

]

and Bax [(1.48±0.08) 

vs

(2.25±0.10)

P

<

0.01)

]

.       Conclusion        Ex-4 can inhibit EPBS-induced apoptosis in HUVECs through down-regulating the expression of ER stress-related proteins such as calnexin

CHOP and Bax.