脱氢表雄酮抑制高脂诱导的兔主动脉及人脐静脉内皮细胞细胞间黏附分子1的表达

摘要

目的:探讨脱氢表雄酮对高脂诱导的兔主动脉及人脐静脉内皮细胞细胞间黏附分子1(ICAM-1)表达的影响,以及全反式维甲酸(ATRA)在这一过程中的作用.方法:细胞实验:将培养的人脐静脉内皮细胞(HU-VECs)分为正常对照组、氧化型低密度脂蛋白(ox-LDL)组、ox-LDL+DHEA组、ox-LDL+DHEA+ATRA组和DHEA组.各组细胞均加入相应药物作用24 h,采用RT-PCR和细胞酶联免疫吸附法检测各组细胞ICAM-1 mRNA及蛋白的表达情况.动物实验:将大耳白兔分为正常对照组、高脂组、高脂+DHEA组、高脂+DHEA+ATRA组和DHEA组.各组白兔均用相应饲料喂饲10周后处死动物,采用RT-PCR和免疫组织化学等方法检测各组白兔主动脉ICAM-1的mRNA及蛋白的表达情况.结果:细胞实验:ox-LDL 组 ICAM-1的表达明显高于正常对照组(P <0.05);与ox-LDL组相比,ox-LDL+DHEA组ICAM-1的表达明显降低(P<0.05);DHEA组与正常对照组ICAM-1的表达无显著差异(P>0.05); ox-LDL+DHEA+ATRA组与ox-LDL+DHEA组ICAM-1的表达无显著差异(P>0.05).动物实验:高脂组主动脉ICAM-1的表达明显高于正常对照组(P<0.05);与高脂组相比,高脂+DHEA组ICAM-1的表达明显降低(P<0.05);DHEA组与正常对照组ICAM-1的表达无显著差异(P>0.05);高脂+DHEA+ATRA组与高脂+DHEA组ICAM-1的表达无显著差异(P>0.05).结论:DHEA能够抑制高脂诱导的兔主动脉及人脐静脉内皮细胞ICAM-1的表达,这可能是其抗动脉粥样硬化的机制之一,而全反式维甲酸对DHEA的这一作用并无明显增强作用.%AIM:To investigate the effects of dehydroepiandrosterone(DHEA)on the expression of intercellu-lar adhesion molecule-1(ICAM-1)induced by high lipid levels in rabbit aorta and human umbilical venous endothelial cells(HUVECs),and the effects of all-trans retinoic acid(ATRA)in this process.METHODS: For in vitro experi-ments,the cultured HUVEC were divided into control group,oxidized low-density lipoprotein(ox-LDL)group,ox-LDL+DHEA group,ox-LDL+DHEA+ATRA group and DHEA group.The HUVECs in all groups were treated with the corre-sponding reagents for 24 h.The expression of ICAM-1 at mRNA and protein levels in all groups were determined by RT-PCR and ELISA,respectively.For in vivo experiments,the rabbits were divided into control group,high lipid group,high lipid+DHEA group,high lipid+DHEA+ATRA group and DHEA group.The rabbits in all groups were fed with the cor-responding diets for 10 weeks.The expression of ICAM-1 in the rabbit aorta at mRNA and protein levels was determined by RT-PCR and immunohistochemistry.RESULTS:The expression of ICAM-1 in the HUVECs in ox-LDL group was signifi-cantly increased compared with control group(P<0.05).Compared with ox-LDL group,the expression of ICAM-1 in ox-LDL+DHEA group was obviously decreased(P<0.05).The expression of ICAM-1 was similar in both control group and DHEA group(P>0.05).The expression of ICAM-1 was similar in both ox-LDL+DHEA group and ox-LDL+DHEA+ATRA group(P>0.05).The expression of ICAM-1 in the rabbit aorta in high lipid group was significantly increased com-pared with control group(P<0.05).Compared with high lipid group, the expression of ICAM-1 in high lipid+DHEA group was obviously decreased(P<0.05).No remarkable difference in the expression of ICAM-1 between control group and DHEA group was observed(P>0.05), so did between high lipid +DHEA group and high lipid +DHEA+ATRA group(P>0.05).CONCLUSION:DHEA inhibits high lipid-induced ICAM-1 expression in rabbit aorta and HUVECs. That may be one of the mechanisms of antiatherosclerotic effect of DHEA.ATRA seems no positive effect on DHEA func-tion.