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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

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

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【作者】 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

【Author】 DAI Shun-Ling, DUAN Jin-Hong, LU Yuan, ZHANG Yi-Hua, CHENG Jin-Xuan, ZHAO Xiao-Yuan 1, WU Yun-Qing, ZHANG Yan-Dong, YU Yue, ZHANG Ling, ZUO Ping-Ping,WU Yi-Yong 2, GE Qin-Sheng 3 (Faculty of Basic Medicine,Peking Union Medical College, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences, Beijing 100005; 1.Capital Insitute of Pediatrics, Beijing 100021; 2.Department of Obstetric and Gynecology, Beijing Hospital,Beijing 100730; 3.Department of Obstetric and Gynecology, Peking Union Medical College Hospital, Beijing 100730, China)

【机构】 中国协和医科大学基础医学院中国医学科学院基础医学研究所首都儿科研究所北京医院妇产科北京协和医院妇产科 北京100005北京100005北京100021北京100730北京100730

【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

【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.

【基金】 国家自然科学基金 (39870 342 );卫生部基金 (96 0 2 0 13和 98 0 1 0 2 0 )资助
  • 【文献出处】 中国动脉硬化杂志 ,Chinese Journal of Arterial Lerosis , 编辑部邮箱 ,2003年05期
  • 【分类号】R543.5
  • 【被引频次】30
  • 【下载频次】132
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