新的植物雌激素α玉米赤霉醇明显抑制实验性动脉粥样硬化发病进程
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国家自然科学基金(39870342);卫生部基金(9602013和9801020)资助


A New Phytostrogen α-Zearalanol Markedly Inhibits the Progression of Experimental Atherogenesis
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    摘要:

    雌性激素具有抗动脉粥样硬化作用,但具有明显的副作用,近年争议尤甚。我们发现了一种新的植物雌激素α玉米赤霉醇,并于1996年首次引进医学研究领域。为了探讨α玉米赤霉醇抗动脉粥样硬化与改善脂质代谢的作用并与雌激素进行比较,将6 0只新西兰成熟未孕兔分成7组:正常对照组6只,普通饲料喂养;假手术组8只,作假手术;高脂对照组10只,小剂量玉米赤霉醇组8只,中剂量玉米赤霉醇组10只,大剂量玉米赤霉醇组8只,雌二醇组10只;上述各组除正常对照组和假手术组外,均作了卵巢摘除术;除正常对照组外均喂高脂饲料12周。在实验开始时和第4、8、12周时分别测定血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白Al和B。实验结束时处死动物,取主动脉标本,油红O染色,肉眼观察并用扫描仪测定兔主动脉内膜脂质斑块沉积面积与主动脉内膜总面积之比,另取小块主动脉常规切片作病理观察。结果发现,主动脉内膜脂质斑块与内膜总面积之比,正常对照组为0 .0 2±0 .0 0 3;假手术组为0 .42±0 .15 ;高脂对照组为0 .6 7±0 .2 3;小剂量玉米赤霉醇组为0 .6 1±0 .13;中剂量玉米赤霉醇组为0 .10±0 .0 6 ;大剂量玉米赤霉醇组为0 .32±0 .10 ;雌二醇组为0 .12±0 .11;后3组与高脂对照组比较,差异有极显著性统计学意义(P<0 .0 1)。病理观察发现,正常对照组内皮正常完整,未见泡沫细胞;高脂对照组内皮脱落、坏死、大量泡沫细胞,可见液化坏死及钙化点、内弹力板明显外移;假手术组、中剂量玉米赤霉醇组、大剂量玉米赤霉醇组和雌二醇组上述病理变化明显减轻,仅有少量泡沫细胞,内皮基本正常。还发现高脂对照组血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇和载脂蛋白B明显升高,而假手术组、小、中、大剂量玉米赤霉醇组和雌二醇组均有下降,以中、大剂量玉米赤霉醇组和雌二醇组明显。此结果提示,α玉米赤霉醇可减少主动脉内膜脂质斑块沉积,改善脂质代谢障碍,改善高脂血症,减轻病理变化。α玉米赤霉醇具有强有力的抗动脉粥样硬化作用,此作用与17β雌二醇相似。

    Abstract:

    Aim and Background The beneficial effect of estrogen on atherosclerosis and related cardiovascular disease has been recognized, however there were obvious adverse side effect recently. This controversy were continued more intensely. We found a new phytoestrogen α-Zearalanol (ZAL). Our lab first brought ZAL into medical research field to study its antiatheorsclewsis effect. To examine the effect on atherosclerosis (As) development and serum lipid prolife, and in comparison with estrogen, in order to provide a basic materials for future study. Methods Sixty adult female New-Zealand rabbits were divided into 7 groups: normal control (NC)group (n=6), sham-operated (SO) group (n=8),high-cholesterol control(HCC) group (n=10), small dose ZAL (SDZ) group (n=8), medium dose ZAL (MDZ) group (n=10),large dose ZAL (LDZ) group (n= [WT5”BZ]8), 17β-estrogen (E2) group (n=10). All groups except NC group and SO group were treated with oophoretomy; all groups except NC group were fed with high-cholesterol for 12 weeks. At week 0, 4, 8, and 12,the serum lipid TC, TG, HDLC, LDLC, apolipoprotein Al and B were measured. At feeding cholesterol week 12 the area of aortic intima lipid plagues to total area of aortic intima were evaluated by scanner and the pathologic changes were observed. Results The ratio of area of aortic lipid plaque to total area of aortic intima in NC group was 0.02±0.003, in SO group was 0.42±0.15, in HCC group was 0.67±0.23, in SDZ group was 0.61±0.13, in MDZ group was 0.10±0.06, in LDZ group was 0.32±0.10, in E2 group was 0.12±0.11 (SO group, MDZ group, LDZ group, and E2 group four groups are compared with HCC group,p<0.01). The serum contents of TC, TG, LDLC, apolipoprotein B in HCC group was siginificantly increased compared with the SO group, while those in MDZ groups, LDZ group, and E2 group, were significantly decreased compared with HCC group. The pathologic changes showed in NC group intact endothelial cell. In HCC group it showed severe endothelial cell damaging and falling off, liquid like necrosis, obvious outward shifting of intimal elastic layer, a large amount of foam cell and lipid plaque, necrosis and calcification. In SO group, in MDZ groups, LDZ group, and E2 group, aforementioned pathological atteration were significantly attenuated. Conclusion Administration of ZAL can decrease the area of aortic lipid plaque and markedly reduce the pathological changes and participate improvement and regulation of disturbance of lipid metabolism including the degree on hyperlipidemia. Phytoestrogen ZAL has a potentially importment antiatherogen effect. Analogous to that observed with 17β-estrogen in this model.

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戴顺龄,段金虹,陆媛,张仪华,程锦轩,赵小元,吴云清,张彦东,余跃,张琳,左萍萍,吴宜勇,葛秦生.新的植物雌激素α玉米赤霉醇明显抑制实验性动脉粥样硬化发病进程[J].中国动脉硬化杂志,2003,11(5):385~390.

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  • 收稿日期:2002-11-04
  • 最后修改日期:2003-06-10
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