关键词: 动脉粥样硬化, 脱氢表雄酮, 细胞色素P450芳香酶基因, 基质金属蛋白酶-9, 人脐静脉内皮细胞

Abstract: Objective To investigate the effect of DHEA on antiatherosclerosis and its mechanisms. Methods In vitro cultured HUVEC were divided into 6 groups: control group; ox-LDL group (30 mg/L ox-LDL); DHEA (low and high concentration) intervention group (30 mg/L ox-LDL + 0.1 and 1 μmol/L DHEA); DHEA＋ATRA intervention group (30 mg/L ox-LDL + 1 μmol/L DHEA + 0.01 μmol/L ATRA); DHEA group (1 μmol/L). The expressions of HUVEC MMP-9 mRNA and protein were determined by RT-qPCR and ELISA respectively. The eukaryotic expression plasmid pcDNA3.1-CYP19-GFP (CYP19) and pcDNA3.1-GFP were transfected into HUVEC respectively. The transfected HUVEC were treated with ox-LDL and DHEA. The expressions of MMP-9 mRNA and protein of transfection groups were determined by RT-qPCR and ELISA. Rabbits were divided into 5 groups: control group; high lipid group (oral 1％cholesterol and 3％lard oil); DHEA intervention group (oral 0.27% DHEA); DHEA＋ATRA intervention group (oral 0.6 mg/kg?d ATRA); DHEA group. The expressions of aortic MMP-9 mRNA and protein were determined by RT-qPCR and immunohistochemistry. Results The expression of MMP-9 in HUVEC in ox-LDL group was significantly increased as compared with control group (P<0.05); The expressions of MMP-9 in DHEA (low and high concentration) intervention groups were obviously decreased in a dose-dependent manner (P<0.05). The expression of aortic MMP-9 in high lipid group was significantly increased as compared with control group (P<0.05). Compared with high lipid group the expression of MMP-9 in DHEA intervention group was obviously decreased (P<0.05). The expression of MMP-9 in CYP19+ox-LDL+DHEA group was significantly decreased as compared with empty plasmid+ox-LDL+DHEA group (P<0.05). Conclusions DHEA inhibits high lipid induced MMP-9 expression in rabbit aorta and HUVEC. CYP19 over-expression can enhance the effect of DHEA.

Key words: artherosclerosis, dehydroepiandrosterone, CYP19, matrix metalloproteinase-9, human umbilical venous endothelial cells