Objective        To determine the effects of exogenous apelin-13 peptide on the formation of atherosclerosis in rats

and investigate its possible underlying mechanisms.         Methods        A total of 60 SD rats (7 to 8 months old

weighing 170 to 220 g) were randomly divided into 4 groups (n=15)

that is

normal control group (group N

fed with normal diet)

model group (group M

fed with high fat diet

every 2 d given normal saline through caudal vein)

low-dose apelin-13 group (group LA

fed with high fat diet

every 2 d receiving 2 mg/kg apelin-13 through caudal vein)

and high-dose apelin-13 group (group HA

fed with high fat diet

every 2 d given 8 mg/kg apelin-13 through caudal vein). In the beginning of high-fat feeding

the rats of latter 3 groups were injected intra-peritoneally with 60×10

4

U/kg vitamin D3 for one time. At the end of 12 weeks’ feeding

the rats’ blood samples were harvested for their serum lipids levels

malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in each group. Ultrasound examination was used to observe abdominal aortic lesions. After all rats were killed

their aortic arches were collected. HE staining was employed to observe the morphological changes of artery tissue

immunohistochemical assay to detect the expression of smooth muscle actin (α-SMA) and p22phox

and Western blotting to detect the expression of p22phox

NF-κB p65

JNK and p-JNK.         Results        Compared with group N

the lipids of the other 3 groups were significantly increased besides HDL-C (P0.01). The MDA content was significantly lower

while SOD activity was higher in group LA and group HA than in group M

with those in group HA more significant (P0.01). HE staining indicated that the group M and group LA had significantly thickened and unsmooth intima in the aortic arch

with many fibrosis plaques

inflammatory cells infiltration

cholesterol crystal and calcification

suggesting ob

vious typical signs of atherosclerosis. In HA group

the slightly thickened intima was a little less smooth

and smooth muscle cells arranged in a little disorder

with few fibrosis and inflammatory cells infiltration. Ultrasonic detection showed that abdominal aorta intima was less clear

rough

discontinuous and thickened

and even small proliferous plaques in the lumen in group M and group LA. Immunohistochemical staining showed that the expression of α-SMA in the aorta were significantly lower in the other 3 groups than in group N (P0.01)

and those of group M and group HA was significantly higher than that in group LA (P0.01). The expression of p22phox was significant lower in group LA and group HA with group M（P0.01）

with the HA group lowest. Western blotting showed that the expression of p22phox

NF-κB p65 and p-JNK were significantly higher in the other 3 groups than in group N (P0.01). Compared with group LA and group HA，expression of p22phox

NF-κB p65 of group M was significantly higher（P0.01); p-JNK expression had no significant difference among group LA

group HA and group M (P0.05)；The expression of p22phox

NF-κB p65 and p-JNK was lower in group HA than in group LA (P0.01); JNK expression showed no significant difference between group LA and group M (P0.05).         Conclusion        Exogenous apelin-13 peptide reduces the oxidative stress effects in the formation of atherosclerosis in rats

and inhibits smooth muscle cell proliferation

which might be through preventing the activation of JNK/NF-κB signaling pathway.