植物雌激素α-玉米赤霉醇与17β雌二醇、戊酸雌二醇对兔食饵性动脉粥样硬化的作用

Effects and Mechanism of A New Phytoestrogen α-Zearalanol,17β-estradiol and estradiol valerate on Experimental Atherosclerosis in cholesterol fed rabbits

目的:研究新的植物雌激素α-玉米赤霉醇(α-ZAL)的抗动脉粥样硬化(AS)作用。方法:49只新西兰成熟未孕雌兔分成6组。A组为正常对照组;B组为假手术组;C组为高脂对照组;D组为17βE2雌二醇组;E组为戊酸雌二醇组;F组为α-ZAL组。分别测定血清TC,LDL-C,HDL-C含量和血浆ET-1及NO水平,肉眼观察并用扫描仪测定各组主动脉内膜脂质斑块沉积面积与内膜总面积之比。并进行病理组织学观察。测定子宫重量/体重。结果:主动脉内膜脂质斑块沉积与内膜总面积之比为B、D、E、F组vs C组P<0.01。病理观察:C组内皮脱落和大量泡沫细胞;B、D、E、F组上述病理变化明显减轻,内皮基本正常或正常,仅有少量或无泡沫细胞。子宫重量/体重D、E、F组较C组明显增加,但F组增加明显小于D组、E组。血清TC、LDL-C、C组均明显升高,而B、D、E、F组明显低于C组,HDL-C各组无显著差异;血浆ET-1与NO水平C组明显升高,而B、D、E、F组明显下降。结论:α-ZAL可减少主动脉内膜脂质斑块沉积面积,减轻病理变化,减轻高脂血症,降低增高的ET-1与过度增高的NO,具有较强的抗AS作用。但对子宫增大作用明显小于17βE2与E2V。

Objective: To investigate the effect of α-zearalanol(α-ZAL) on antiatherosclerosis and in comparison with 17β-estradiol (17βE_ 2 ) and estradiol valerate (E_ 2 V) in order to provide basic materials for future study.Method: Forty-nine adult virginal female new Zealand rabbits were divided into 6 groups.Group A: normal control group;group B: sham operated group;group C: untreated high cholesterol group;group D: 17βE_ 2 group;group E: E_ 2 V group;group F: α-ZAL group.CHO fed for 12 weeks at before CHO fed and at CHO fed week 12,the serum lipid TC、 LDL-C、 HDL-C were measured.At CHO fed week 12,the plasma ET-1 level was measured by RIA,the plasma NO(NO_ 2- )level was measured by gresis method.The ratio of area of aortic intima lipid plaque deposition to total area of aortic intina was evaluated by scanner,and patholoaical changes were observed.The uterine weight body weight(g Kg) was monitored.Results: Significant differences could be found at the ratio of area of aortic intima lipid plaque to total area of aortic intima (group B、D、E、F vs C,P<0.01).The pathological changes showed as follows:in group A: intact endothelial cell layer; in group C: severe endothelial cell.Group B、D、E、F:obvious improvement of pathological changes,nearly normal endothelial cells,few or no foam cells.The uterine weight body weight(g Kg) of group D、E and F was significantly higher than that of Group C.But group F was markedly lesser than that of group D and E.The serum content of TC,LDL-C,plasma ET-1 and NO(NO_ 2- ) in group C were significantly increased compared with group B、D、E、F.Conclusion: Administration of α-ZAL can markedly decrease the area of aortic lipid plaque,reduce the pathological alteration,lighten the degree of hyperlipidemia and decrease plasma ET-1 and NO_ 2- level.α-ZAL has a potentially important antiatherogenic effect analogous to that of 17βE_ 2 and E_ 2 V_ in the study.But its hyperstrophic effect on uterine was significantly lesser than that of 17βE_ 2 and E_ 2 V.