早期雌激素替代治疗对兔动脉粥样硬化和血浆PAI-1的影响

目的:了解早期经皮雌激素替代治疗(estrogen replacement therapy ,ERT)对高脂喂养的去势雌兔动脉粥样硬化和纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1, PAI-1)水平的影响.方法:28只兔随机分为4组:A组为假手术对照组;B组为单纯去势组;C组为去势 小剂量ERT组;D组为去势 大剂量ERT组.4组均给予高脂饮食12周,分别于术前、高脂喂食4周和12周后抽血,测定血脂、雌二醇和PAI-1.实验结束后,分离主动脉标本行组织形态学观察.结果: 12周后B组血清雌二醇浓度明显低于A组(P＜0.01),D组明显高于A组(P＜0.01),C组与A组间无统计学差异(P＞0.05);12周后B组血清TC,LDL-C水平显著高于A组(P＜0.01);C,D组的血清TC,LDL-C水平均低于A组(P＜0.01),而B组的TG,HDL-C水平均低于其余3组.B组PAI-1的水平显著高于A,C,D组(P＜0.01).而A,C,D组之间PAI-1水平的变化无统计学差异.B组主动脉粥样斑块面积明显大于A,C及D组(P＜0.01), C,D两组的斑块面积小于A组(P＜0.01).结论:早期经皮雌激素替代治疗可改善血脂代谢、降低PAI-1水平、抑制兔动脉粥样硬化形成.

Effect of estrogen replacement therapy in the early phaseon atherosclerosis and PAI-1 in ovariectomizedcholesterol-fed rabbits

Objective To investigate the effect of estrogen replacement therapy (ERT) in the early phase on the atherosclerosis and the level of plasminogen activator inhibitor-1(PAI-1). Methods Twenty-eight rabbits were randomly assigned to 4 groups: Group A, sham operation (n=7); Group B, ovariectomized without estradiol (n=7); Group C, ovariectomized with low-dose estradiol (n=7); and Group D, ovariectomized with high-dose estradiol (n=7). All rabbits were given 1% cholesterol diet for 12 weeks. Levels of blood lipid, estradiol, and PAI-1 were measured before the operation and at the end of the 4th and 12th weeks. Twelve weeks later, we took the aortas for pathological analysis and calculated the areas of atherosclerotic plaque. Results After 12 weeks, the estradiol level of Group B was significantly lower than that of Group A, and that of Group D was obviously higher than Group A. There was no significant difference between Group C and A. The concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in Group B significantly increaseed compared with Group A (P<0.01). The levels of TC and LDL-C of Group C and D were significantly lower than those of Group A. Whereas the concentrations of triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) in Group B were lower than those of Groups A,C, and D (P<0.01). In contrast to Groups A, C, and D,the level of PAI-1 was significantly higher in the Group B (P<0.01), without significant differences among Groups A, C, and D. The area of atherosclerotic lesion of aorta in Group B was significantly bigger than that of Group A, C, and D. The areas of aortic atherosclerotic plaque in Group C and D were obviously smaller than those of Group A (P<0.01). Conclusion Transdermal estrogen replacement therapy in the early phase can improve the metabolism of the serum lipids, reduce the level of PAI-1, and probably provide the protective effect on the atheroma formation.