早期给予雌激素对去卵巢兔动脉斑块及血脂、单核细胞趋化蛋白1的影响

The Effects of Early Estrogen Replacement Therapy on Atherosclerotic Lesions,Serum Lipid and Monocyte Chemoattractant Protein-1 Levels in Ovariectomized Rabbits

目的观察早期不同剂量雌激素替代治疗对高脂饮食诱导的去卵巢雌兔动脉粥样硬化及血脂、单核细胞趋化蛋白1的影响。方法健康雌性新西兰白兔28只,随机分为假手术组、去卵巢组、去卵巢+小剂量雌激素替代治疗组(苯甲酸雌二醇200μg)和去卵巢+大剂量雌激素替代治疗组(苯甲酸雌二醇1mg)。术后给予高脂饲料喂养,测定血清总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、雌二醇和单核细胞趋化蛋白1浓度,并分离主动脉标本行组织形态学观察。结果与假手术组比较,去卵巢组高脂喂食后血清总胆固醇、低密度脂蛋白胆固醇、单核细胞趋化蛋白1均明显升高,血清高密度脂蛋白胆固醇、雌二醇水平下降;而雌激素替代治疗组的上述指标与假手术组相似;与小剂量雌激素替代治疗组比较,大剂量雌激素替代治疗组12周后雌二醇水平较高、单核细胞趋化蛋白1水平较低。比较主动脉斑块面积,去卵巢组大于假手术组,而雌激素替代治疗两组明显小于去卵巢组和假手术组,但雌激素替代治疗两组之间差异无显著性。主动脉斑块面积与高脂喂养12周后血清低密度脂蛋白胆固醇、总胆固醇以及单核细胞趋化蛋白1水平呈明显正相关(r分别为0.765,0.803,0.829,P均<0.01),与血清高密度脂蛋白胆固醇(r=-0.441,P<0.05)、雌二醇水平呈负相关(r=-0.755,P<0.01)。结论早期雌激素替代治疗可改善血脂代谢、降低单核细胞趋化蛋白1水平、减少主动脉斑块面积。雌激素的调脂、抗炎作用可能与其抗动脉粥样硬化作用有关。

Aim To investigate the effects of early estrogen replacement therapy （ERT） of different doses on atherosclerotic lesions, serum lipid and monocyte chemoattractant protein-1 （MCP-1） levels in ovariectomized fat-fed female rabbits. Methods Twenty-eight female New Zealand White rabbits were randomly divided into sham operation group, ovariectomized group, ovariectomized with low-dose ERT group （estradiol benzoate 200 μg） and ovariectomized with high-dose ERT （ estradiol benzoate 1 mg） group. All rabbits were given high-fat diets after the surgery for 12 weeks. The levels of serum total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （ HDLC ）, estradiol and MCP- 1 were measured. 12 weeks later, the aortas were taken for pathological analysis and for calculating the areas of atherosclerotic plaques. Results Compared with sham operation group, the serums levels of TC, LDLC and MCP-1 in ovariectomized group were significantly increased after high-fat diet for 12 weeks, meanwhile the serum levels of HDLC and estradiol were decreased. But the above indexs had no differences between ERT groups and sham operation group. Compared with low-dose ERT group, high-dose ERT group had higher levels of estradiol and lower levels of MCP- 1. After high-fat diet for 12 weeks, the extent of atherosclerotic lesions of aorta in ovariectomized group was remarkably bigger than that in sham operation group. The extent in both ERT groups was significantly smaller than that in sham operation group and ovariectomized group. There were no statistical difference in the aortic lesions among two ERT groups. The areas of atherosclerotic plaque were positively correlated with the serum levels of LDLC, TC, and MCP-1, but negatively correlated with the serum levels of HDLC and estradiol. Conclusions Early ERT can modulate the blood lipid, decrease the serum levels of MCP-1 and reduce the areas of atherosclerotic plaque. The antiatherogenic effect of early ERT may be associated with its effects of ameliorating the lipid metabolism and anti-inflammation.