Effects of selenium supplement on atherogenesis of ApoE-knockout mice fed high fat diet

Abstract

To investigate the effects of selenium supplement on atherogenesis and endothelial function in ApoE-knockout mice fed high fat diet. ApoE-knockout mice fed with selenium-deficient and high fat diet were randomly allocated into 3 groups based on random number table including control group (not supplied with sodium selenite, n=10), low dosage selenium supplement group (supplied water with 0.1 mg/L sodium selenite, n=10) and high dosage selenium supplement group (supplied water with 0.2 mg/L sodium selenite, n=10). After 15 weeks, the following values were measured: the concentrations of selenium in heart and liver, the levels of serum lipid, the parameters of antioxidant function including activities of superoxide dismutase(SOD) and glutathion peroxidase (GSH-Px) and malondialdehyde (MDA) level in serum, the parameters of endothelial function including serum nitric oxide (NO), endothelin 1(ET-1), and vascular endothelial growth factor (VEGF) levels, and ET-1 and VEGF levels in aorta roots. The atherosclerotic lesions in aorta roots were analyzed with oil red O staining. (1) The selenium concentrations in heart and liver were significantly higher in high dosage and low dosage selenium supplement groups compared to control group (both P<0.05). (2) The levels of triglyceride, total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and high-density lipoprotein cholesterol were similar among groups (all P>0.05). (3) The activity levels of serum SOD were significantly higher in low dosage ((113.8±12.5)U/ml) and high dosage selenium supplement group ((152.3±11.3)U/ml) compared to control group ((90.7±10.7)U/ml, all P<0.05). The activity levels of serum GSH-Px were significantly higher in low dosage ((53.9±7.2)U/ml) and high dosage ((69.6±8.7)U/ml) selenium supplement groups than that of control group ((36.4±5.6)U/ml, all P<0.05). The serum MDA levels in low dosage ((4.73±1.05)nmol/ml) and high dosage ((4.13±1.21)nmol/ml) selenium supplement groups were significantly lower than that of control group ((5.97±1.08)nmol/ml, all P<0.05). (4) The serum NO concentrations in low dosage ((61.5±12.8)μmol/L) and high dosage ((79.0±14.6)μmol/L)selenium supplement groups were significantly higher than that of control group((42.7±9.1)μmol/L, all P<0.05). The concentrations of serum ET-1 in low dosage ((52.8±6.3)ng/L)and high dosage ((46.3±4.7)ng/L)selenium supplement groups were significantly lower than that of control group((72.2±6.3)ng/L, P<0.05). The concentrations of serum VEGF in low dosage ((97.4±16.5)ng/L)and high dosage ((83.5±22.0)ng/L)selenium supplement groups were significantly lower than that of control group((125.8±18.6)ng/L, P<0.05). The expression levels of ET-1 and VEGF in aorta roots among low dosage and high dosage selenium supplement groups were significantly lower compared to control group (all P<0.05). (5) The plaque area of aorta roots in low dosage ((0.95±0.19)×10(5) μm(2))and high dosage selenium supplement ((0.75±0.15)×10(5) μm(2)) groups were significantly smaller than that of control group((1.13±0.23)×10(5) μm(2)), and the plaque area in high dosage selenium supplement group was significantly smaller than in low dosage selenium supplement group (P<0.05). Supplement of selenium can attenuate atherogenesis in ApoE-knockout mice fed high fat diet, which is possibly mediated via reducing lipid peroxidation and improving endothelial functions.