木豆叶芪类提取物及其合成类似物调节胆固醇代谢和血管保护作用的机制研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
动脉粥样硬化(atherosclerosis,AS)是心脑血管疾病最重要的发病因素。在动脉粥样硬化的诱发因子中,高脂血症是一个主要的独立危险因素。所以从药用植物中寻找具有降血脂作用的天然化合物,并研究其作用机理是近年来的研究热点,具有重大的应用前景和社会效益。在对高脂血脂诱发动脉粥样硬化的研究中发现,低密度脂蛋白胆固醇(low density lipoprotein-cholestero,LDL-C)是主要的致病因子之一。近期的研究表明胆固醇的逆向转运过程(reverse cholesterol transport,RCT)在改善血脂代谢,防治动脉粥样硬化中的作用越来越重要。RCT过程能够促进外周组织胆固醇的清除,降低体内胆固醇水平,延缓动脉粥样硬化的发生和发展。
     本课题组在既往的研究中发现,豆类植物木豆的叶子提取物能明显降低动物的体重和血糖水平。木豆叶总提取物中主要包含芪类成分和黄酮类成分,可用于治疗妇女更年期综合症、防治骨质疏松、降低血糖。但是,关于木豆叶提取物调节胆固醇代谢的研究目前还没有报道。本课题在国内外首次以木豆叶提取物为干预药物,观察芪类成分及其合成类似物S03、黄酮类成分调节体内胆固醇代谢,促进RCT过程的机理,并探讨它们抗动脉粥样硬化形成的潜在作用。
     1.木豆叶提取物及其合成类似物S03对高脂血症模型动物血脂代谢的影响
     首先通过手术去除动物卵巢的方式建立高脂血症模型模拟绝经后女性血脂变化,初步了解木豆叶总提取物对该模型的治疗作用。研究发现木豆叶总提取物具有降低动物血脂和血糖水平的趋势。为进一步明确木豆叶总提取物中具有调节胆固醇代谢作用的有效成分,通过喂食高脂饲料的方式建立高脂血症动物模型,分别给予木豆叶芪类成分和黄酮类成分,观察两类成分调节血脂的效应和作用机理。研究结果表明黄酮类成分对于血脂代谢无明显影响。而木豆叶芪类提取物却具有明显的血脂调节功能,能够减轻动物体重,显著降低高脂模型小鼠血清总胆固醇(TC)、甘油三酯(TG)和LDL-C水平,提高血清超氧化物歧化酶(SOD)的活力。同时芪类成分还可以明显减少肝脏中TC和TG的蓄积。为探讨芪类物质的作用机制,选择肝脏中涉及胆固醇合成、吸收和代谢的三个关键蛋白-HMG-CoA R、LDL-R和CYP7A1作为观察对象,以RT-PCR的方法检测其表达水平。结果表明,芪类成分可以上调这三者的基因表达,通过促进LDL-C的吸收和增加胆固醇向胆汁酸转化来降低体内胆固醇水平。
     同时,在实验中还观察到芪类成分的合成类似物S03可以改善去卵巢高脂血症模型动物的血脂代谢。去卵巢手术后动物体重和血清胆固醇含量异常升高,S03可以明显减轻去卵巢动物体重和肝脏重量,减少动物血清中TC含量和LDL-C含量。此外,S03还可以降低动物体内卵泡刺激素(FSH)和促黄体生成素(LH)的浓度,纠正去卵巢后的性激素分泌失调。
     2.木豆叶芪类单体成分C03对胆固醇逆向转运过程的影响
     根据前一个实验结果,选择芪类成分中的单体成分C03作为观察药物,了解其对RCT过程的影响。巨噬细胞中胆固醇通过ABCA1流出是RCT过程的起始步骤。同时,由巨噬细胞大量摄取氧化低密度脂蛋白转化成的泡沫细胞,也是动脉粥样硬化斑块的重要组成部分。肝脏细胞中含有的LDL-R和SR-BⅠ介导了RCT过程的终止步骤。本实验确定上述在RCT过程起始和终止阶段的重要功能蛋白作为观察对象,检测C03对胆固醇逆向转运过程中ABCA1、LDL-R和SR-BⅠ蛋白功能和表达的影响,以及C03抑制巨噬细胞内胆固醇蓄积,减少泡沫细胞形成的效应。
     结果显示C03可以上调巨噬细胞中ABCA1的表达,促进巨噬细胞内[~3H]胆固醇的流出,有助于启动RCT过程。同时还发现C03可以抑制巨噬细胞对氧化低密度脂蛋白的吞噬摄取,降低细胞内的总胆固醇含量和胆固醇酯含量,进而抑制泡沫细胞的形成。C03能够显著上调肝脏细胞中LDL-R的表达,且该作用具有剂量依赖性和时间依赖性。对于SR-BⅠ的表达,C03的作用并不明显。研究表明C03不但可以促进RCT过程,而且具有防治动脉粥样硬化脂质斑块形成的功能,有益于减缓动脉粥样硬化的病理改变。
     此外,根据已有的实验结果,采用受体结合实验来了解C03与肝脏雌激素受体的结合特性,观察C03与雌激素受体结合的有关常数。为深入探讨C03的作用机制奠定基础。
     3.木豆叶芪类成分C03及其合成类似物S03血管保护作用的初步研究
     氧化损伤是血管内皮细胞损伤的重要因素之一,而内皮细胞的损伤和功能改变是动脉粥样硬化的始动因素。本部分实验采用过氧化氢损伤人脐静脉血管内皮细胞株(EAhy926细胞)建立内皮细胞过氧化损伤模型,观察C03对过氧化氢损伤的拮抗作用,同时了解C03改善血管内皮细胞功能的效应。结果表明C03可以降低过氧化氢对EAhy926细胞的损伤,提高细胞的存活率。C03抗氧化、保护血管内皮细胞的作用可能是通过提高细胞内超氧化物歧化酶的活性,同时增加细胞的NO分泌量来达到的。
     在动脉粥样硬化形成过程中,动脉内皮发生损伤诱导血管平滑肌细胞增殖,参于炎症反应和斑块纤维帽的形成。本实验通过将C03和S03与血管平滑肌细胞共同培养发现,S03能够剂量依赖性抑制血管平滑肌细胞的增殖,而C03的抑制作用相对较弱,可能具有减弱血管壁增厚的潜能。
     综上所述,本课题建立了两种不同的高脂血症动物模型,分别验证了木豆叶芪类成分及其合成类似物S03改善高脂血症的疗效,并探讨了芪类成分降低体内胆固醇含量的作用机理。然后通过体外细胞实验,进一步探讨芪类成分C03对胆固醇逆向转运过程的干预效果和减缓泡沫细胞形成的作用。同时,对于C03抗氧化、保护血管内皮细胞,以及与雌激素受体的结合特性也做了一定程度的研究。本课题在国内外首次从体内体外两个方面采用不同的模型观察木豆叶芪类成分干预胆固醇代谢的作用和血管保护功能,并明确其产生治疗效应的初步机制。研究结果为发现新型调节胆固醇代谢的药物提供了思路和选择,也将为临床治疗动脉粥样硬化等心脑血管疾病带来新的手段。
Atherosclerosis is the basis of coronary artery disease, one of the most serious diseases in man. Hypercholesterolemia is a dominant risk factor for the development and progression of increasing atherosclerosis and related cardiovascular diseases. Thus, the therapeutic benefits of plant extracts without side effects have been the focus of many extensive studies. Plenty of studies indicate that high serum level of low density lipoprotein cholesterol (LDL-C) is associated with atherosclerosis and an increased risk of coronary heart disease.
     Recently, there are several investigates reveale that reverse cholesterol transport (RCT) is one key mechanism in antiatherosclerosis research. Atheroprotective effect of RCT is attributed to its ability to remove macrophage or peripheral organs redundant cholesterol into liver for degradation and eccrisis. The RCT accelerates the cholesterol cleaning in peripheral organs, decreases the serum cholesterol contents, so it is benefit to the prevention and cure of atherosclerosis.
     Cajanus cajan L.Millsp is the subtropical brush plant, which belongs to adjouns genus of popilionaccae family, grows in the southern part of China. There are two active components in the Cajanus cajan L, i.e. the flavonoids and the stilbenes. The stilbenes component possesses the estrogen-like property, it can been used to treat the osteoporosis, diabetes, climacteric symptom of menopause women. In our previous researches, we find the stilbenes containing extract-fraction from Cajanus cajan L (sECC) could decrease the body weight and blood sugar level. But there has been no report on the effect of sECC on cholesterol metabolism.
     Our research team initiately investigated the hypocholesterolemic effect of medicative extract-fraction from Cajanus cajan L. and synthetical analog (S03) on hypercholesterolemia animal models. We observed the hypocholesterolemic effects of flavonoids component and stilbenes component, respectively. Furtherly, we investigated the auxoaction of stilbenes component on reverse cholesterol transport. Based on the experimental evidences, we evaluated the potential antiatherosclerosis effectes of these compoundes. These resultes will help us to extend the drug actions of medicative extract-fraction from Cajanus cajan L in modify cholesterol metabolism and preservation atherosclerosis.
     1. The hypolipidemic effects of medicative extracts of Cajanus cajan L and synthetical analog on hypercholesterolemia animal model
     Ovariectomy induces obesity and hypercholesterolemia by removing the catabolic action of estrogen. We simulated the hypercholesterolemia in post- menopause women with the ovariectomized mice. We finded the descending tendency in the serum cholesterol and glucose content according with the dosage of the medicative extract-fraction from Cajanus cajan L.
     Diet-induced hypercholesterolemia mice had been used for the assessment of flavonoids extract-fraction or stilbenes extract-fraction with beneficial effects on cholesterol metabolism. The serum lipid profile, the hepatic total cholesterol and triglyceride, and the changes in the gene expressions of the key enzymes responsible for cholesterol homeostasis had been detected. After 4 weeks treatment, the increased serum and hepatic total cholesterol and triglyceride levels were markedly attenuated by sECC, the serum LDL cholesterol content also decreased accompanying with the activity of serum superoxide dismutase was increased in sECC treated mice. The mRNA expressions of HMG-CoA reductase, CYP7A1, and LDL-receptor were significantly enhanced in the mice administered with sECC. sECC's hypocholesterolemic effect may involved the enhancement of hepatic LDL-receptor and CYP7A1 mRNA expression levels. Whereas, there was no conspicuous change occurred in flavonoids component groups.
     In the hypercholesterolemia of the ovariectomized rats, we investigate the effects of the synthetical analog of stilbenes component (S03). The results revealed the S03 decreased the serum total cholesterol and LDL cholesterol contents. Meanwhile, there were marked reduces in the body weight and liver weight in the S03 treated rats. The S03 also decreased the abnormal contents of luteotrophic hormone and follicle-stimulating hormone induced by ovariectomized operation.
     2. The effect of monomer compound of sECC (C03) on the reverse cholesterol transport
     We investigated the effect of monomer compound of sECC (C03) on the reverse cholesterol transport. The usage of C03 could up-regulation the protein expression of the ATP binding cassette transporter A1, following facilitate the [~3H] label cholesterol effluent from the macrophage. C03 also prevented the formation of foam cell by depleted the total cholesterol and cholesterol esters in the macrophage.
     The investigations data indicated that C03 could enhance the protein expression of LDL-receptor in liver cell, this effect displayed the characteristic of dose dependent and time dependence. But, there was no conspicuous change occurred in the expression of scavenger receptor class B type I. So we conclude the C03 may promote the reverse cholesterol transport mainly through accelerating the initial phase.
     We have evaluated the binding property of C03 and the estrogen receptor with the competive receptor binding assay.
     3. The protective effects of C03 and S03 on cultured vascular endothelial cell and vascular smooth muscle cell
     Oxidative damage is an important risk factor for the development and progression of vascular dysfunction. Then, vascular dysfunction is the initiating agent of atherosclerosis. We used an injury model induced by H_2O_2 in EAhy926 cells (human umbilical vein endothelial cell) and assessed the protective effect of C03. The injuries of endothelial cell induced by H_2O_2 were indicated as cell viability, release of NO and the activity of SOD. The results exhibited that C03 could significantly increase cell viability, the increased activity of SOD and secretion of NO also been observed.
     Proliferation of vascular smooth muscle cell (VSMC) represents an essential event in the development of atherosclerosis. The S03 represented significant inhibitory effect on VSMC proliferation. However, C03 has showed lower inhibition on it. These findings suggested that S03 and C03 may arrest the atherosclerosis via the inhibitory effect on VSMC proliferation.
     In a summary, we used different hyperlipoidemia animal models to evaluated the hypolipidemic effect of medicative extract-fraction from Cajanus cajan L and it's synthetical analog. Then, we investigate the accelerating effect of C03 on the reverse cholesterol transport and the effects of C03 and S03 on cultured vascular endothelial cell and vascular smooth muscle cell protection. These results indicated that sECC will be a promising drug for the hypercholesterolemia and atherosclerosis.
引文
[1]“中国胆固醇教育计划(CCEP)”暨卫生部/“十年百项”冠心病血脂干预推广项目年度工作总结会议简介.中国临床医生.2005;33(2):27.
    [2]叶平.积极降脂,有效防治冠心病.老年医学与保健.2005;11(1):11-13.
    [3]Prasad K,Kalra J.Oxygen free radicals and hypercholesterolemic atherosclerosis:effect of vitamin E[J].Am Heart J.1993;125(4):958-973.
    [4]Deepa PR,Varalakshmi P.Atheroprotective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats[J].Clin Chim Acta.2005;355(1-2):119-130.
    [5]Feig JE,Shamir R,Fisher EA.Atheroprotective effects of HDL:beyond reverse cholesterol transport[J].Curr Drug Targets.2008;9(3):196-203.
    [6]胡大一.降胆固醇,防冠心病.中华全科医师杂志.2005;4(2):69-71.
    [7]张庆军,刘德培,梁植权.动脉粥样硬化的基础研究.中华医学杂志.2005;85(6):428-431.
    [8]张红霞,刘剑刚,史大卓.动脉粥样硬化发病机制和炎症反应关系研究进展.中国心血管杂志.2005:10(5):385-387.
    [9]黄广勇,卢才义.动脉粥样硬化血管重塑的认识与研究进展.心血管病学进展.2005:26(6):589-592.
    [10]郑德胜,赵静,巩成翠.动脉粥样硬化危险因素的研究进展.实用心脑肺血管病杂志.2005:13(2):119-121.
    [11]Yokozawa T,Cho EJ,Sasaki S,et al.The protective role of Chinese prescription Kangen-karyu extract on diet-induced hypercholesterolemia in rats[J].Biol Pharm Bull.2006,29(4):760-765.
    [12]Sharma KK,Sreelatha G,Dayal S.Pigeonpea(Cajanus cajan L.Millsp.)[J].Methods Mol Biol.2006;343:359-367.
    [13]韦桂杰,罗平意.浅析木豆种植开发的价值前景.广西林业.2006;1:44-45.
    [14]郑娟.木豆.云南农业.2005;4:7.
    [15]谢金水,付红.木豆的研究动态及利用现状.世界农业,2005,311(3):47-49.
    [16]周永和.浅谈菜食用型印度木豆的推广.云南林业 2004;25(3):20-21.
    [17]王绍明.木豆栽培技术.农村实用技术.2002;12:7-8.
    [18]肖国滨,廖绵清,韩仁道,等.农林复合型作物木豆.今日农村.2002:8:25.
    [19]钟小荣.木豆的利用价值.中药研究与信息.2001,3(8):47。
    [20]孙绍美,宋玉梅,刘俭,等.木豆素制剂药理作用研究.中草药.1995;26(3):147-148.
    [21]刘中秋,周华,林励,等.生脉成骨片中木豆叶提取工艺研究.中成药.1998,20(3):7-9.
    [22]张德兴,王海彬,唐立明,等.综合疗法治疗小儿发育性髋关节脱位手法复位后并发股骨头坏死21例疗效观察.新中医.2006:38(1):52-53.
    [23]Braga FG,Bouzada ML,Fabri RL,et al.Antileishmanial and antifungal activity of plants used in traditional medicine in Brazil[J].J Ethnopharmacol.2007;111(2):396-402.
    [24]黄桂英,廖雪珍,廖惠芳,等.木豆叶水提物抗脑缺血缺氧损伤的作用研究.中药新药与临床药理.2006;17(3):172-174.
    [25]Akinsulie AO,Temiye EO,Akanmu AS,et al.Clinical evaluation of extract of Cajanus cajan(Ciklavit) in sickle cell anaemia[J].J Trop Pediatr.2005;51(4):200-205.
    [26]Ghosh A,Sarkar K,Sil PC.Protective effect of a 43 kD protein from the leaves of the herb,Cajanus indicus L on chloroform induced hepatic-disorder[J].J Biochem Mol Biol.2006;39(2):197-207.
    [27]Duker-Eshun G,Jaroszewski JW,Asomaning WA,et al.Antiplasmodial constituents of Cajanus cajan[J].Phytother Res.2004;18(2):128-130.
    [28]郑元元,杨京,陈迪华,等.木豆叶提取物对人的类成骨细胞TE85成骨功能和体外破骨细胞分化的影响.药学学报.2007,42(4):386-391.
    [29]郑元元,杨京,陈迪华,等.木豆叶芪类提取物对雌激素缺乏性大鼠骨质丢失的影响.药学学报.药学学报.2007,42(5):562-565.
    [1]Goudev A,Kyurkchiev S,Gergova V,etal.Reduced concentrations of soluble adhesion molecules after antioxidant supplementation in postmenopausal women with high cardiovascular risk profiles a randomized double-blind study[J].Cardiology.2000;94(4):227-232.
    [2]Huber J.Phytoestrogens and SERMS,alternatives to classical hormone therapy[J].Ther Umsch.2000;57(10):651-654.
    [3]Wu W H,Kang Y P.Wanc.N H,et al.Sesame ingestion affects sex homones antioxidant status and blood lipids in postmenopausul women[J].J Nutr.2006;136(5):1270-1275.
    [4]Lissin LW,Cooke JP.Phytoestrogens and cardiovascular health[J].J Am Coll Cardiol.2000;35(6):1403-1410.
    [5]包立道,郭秀琴,王玉华,等.蒙药亚苏哈图吉呼对去卵巢骨质疏松小鼠的实验研究.中国民族医药杂志.2006;2:32-33.
    [6]刘波,秦雪,莫武宁,等.雌激素对去势小鼠血脂影响的研究.广西医科大学学报.2005;22(5):716-717.
    [7]段恒,陆华.资冲颗粒灌肠和灌胃对去势小鼠雌激素水平的影响.北京中医药大学学报.2007;30(3):185-187.
    [8]Su S,Hsiao CG,Chu C,et al.Effects of pravastatin on leftventricula mass in patients with hyperlipidemia and essential hypertension[J].Am J Cardiol.2000;86(5):514-518.
    [1]Ballantyne CM.Low-density lipoproteins and risk for coronary artery disease[J].Am J Cardiol.1998;82(9A):3Q-12Q.
    [2]Krieger M.The "best" of cholesterols,the "worst" of cholesterols:a tale of two receptors[J].Proc Natl Acad Sci U S A.1998;95(8):4077-4080.
    [3]Prasad K,Kalra J.Oxygen free radicals and hypercholesterolemic atherosclerosis:effect of vitamin E[J].Am Heart J.1993;125(4):958-973.
    [4]Deepa PR,Varalakshmi P.Atheroprotective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats[J].Clin Chim Acta.2005;355(1-2):119-130.
    [5]陈碧珊,苏丽华.他汀类药物的研究进展.中国药房.2005;16(7):545-546.
    [6]Yokozawa T,Cho EJ,Sasaki S,et al.The protective role of Chinese prescription Kangen-karyu extract on diet-induced hypercholesterolemia in rats[J].Biol Pharm Bull.2006,29(4):760～765.
    [7]钟小荣.木豆的利用价值.中药研究与信息.2001,3(8):47.
    [8]张德兴,王海彬,唐立明,等.综合疗法治疗小儿发育性髋关节脱位手法复位后并发股骨头坏死21例疗效观察.新中医.2006;38(1):52-53.
    [9]Braga FG,Bouzada ML,Fabri RL,et al.Antileishmanial and antifungal activity of plants used in traditional medicine in Brazil[J].J Ethnopharmacol.2007;111(2):396-402.
    [10]Ghosh A,Sarkar K,Sil PC.Protective effect of a 43 kD protein from the leaves of the herb,Cajanus indicus L on chloroform induced hepatic-disorder[J].J Biochem Mol Biol.2006;39(2):197-207.
    [11]Hoekstra M,Out R,Kruijt JK,et al.Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells[J].J Hepatol.2005;42(3):400-407.
    [12]李玉白,赵忠桂,唐明德.喂饲褐藻酸小鼠血脂水平和抗氧化能力的变化.中国临床康复.2006;10(4):80-81.
    [13]Hyun-Dong Paik,Jun-Seok Park,Eunju Park.Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in rats fed a high-fat and high-cholesterol diet [J].Biol. Pharm.Bull.2005; 28 (7) : 1270-1274.
    
    [14]Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues [J]. J Biol Chem. 1957. 226: 497—509.
    
    [15]Moreno J J. The degree of unsaturation of dietary fatty acids and the development ofatherosclerosis[J].J Nutri Biochem.2003; 14 (4): 182-195.
    
    [16]Massberg S, Brand K, Gruner S, et al.A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation [J]. J Exp Med. 2002; 196(7): 887—896.
    
    [17]Steinerova, Racek J, Stozicky F, et al. Antibodies against oxidized LDL theory and clinical use[J]. Physiol Ress.2001; 50 (2): 131 — 141.
    [16]倪敬年,时晶,田金洲.LDL的化学修饰及其致动脉粥样硬化作用.中国老年医学杂志.2006; 11 (26): 1586-1588.
    
    [19]Kwiterovich P O Jr. The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis [J]. J Am Diet Assoc. 1997; 97(7Suppl):S31-41.
    
    [20]Gylling H .Cholesterol metabolism and its implications for therapeutic interventions in patients with hypercholesterolaemia [J]. Int J Clin Pract. 2004; 58(9): 859—866.
    
    [21]Hwang SY, Son DJ, Kim IW, et al. Korean red ginseng attenuates hypercholesterolemia enhanced platelet aggregation through suppression of diacylglycerol liberation in high-cholesterol-diet-fed rabbits[J]. Phytother Res. 2008;22(6): 778-83.
    
    [22]Bertipaglia de Santana M, Mandarino MG, Cardoso JR, et al.Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dyslipidemic subjects[J]. Nutrition. 2008; 24(6):562-568.
    
    [23]Zahid Ashraf M, Hussain ME, Fahim M. Antiatherosclerotic effects of dietary supplementations of garlic and turmeric: Restoration of endothelial function in rats[J].Life Sci.2005; 77(8): 837-857.
    
    [24]Arafa HM. Curcumin attenuates diet-induced hypercholesterolemia in rats[J].Med Sci Monit.2005; 11(7): BR228-234.
    
    [25]Prociuk MA, Edel AL, Richard MN, et al. Cholesterol-induced stimulation of platelet aggregation is prevented by a hempseed-enriched diet[J]. Can J Physiol Pharmacol. 2008; 86(4): 153-159.
    
    [26]Chiang, M T, Chen Y C, Huang, et al.Plasma lipoprotein cholesterol levels in rats fed a diet enriched in cholesterol and cholic acid[J]. Int J Vitam Nutr Res. 1998; 68(5):328-334.
    
    [27]Han KH, Iijuka M, Shimada K, et al. Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7alpha-hydroxylase mRNA levels in rats fed a cholesterol diet [J].Br J Nutr. 2005; 94 (6): 902-908.
    
    [28]Yan LP, Chan SW, Chan AS, et al. Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats [J].Life Sci. 2006; 79 (4): 324—330.
    
    [29]Dhingra S, Bansal MP. Modulation of hypercholesterolemia-induced alterations in apolipoprotein B and HMG-CoA reductase expression by selenium supplementation [J]. Chem Biol Interact. 2006; 161 (1): 49-56.
    
    [30]Ness G C, Gertz K R. Hepatic HMG-CoA reductase expression and resistance to dietary cholesterol[J]. Exp Biol Med. 2004; 229(5): 412—416.
    
    [3 l]Nica M. Borradaile, Linda E DE Dreu, lisa J Wilcox, et al. soya phytoestrogens,genistein and daidzein, decrease apoliporotein B secretion from HepG2 cell through multiple mechanisms[J]. Biochem J. 2002; 366: 531 —539.
    
    [32]Wilcox L J, Barrett P H, Huff M W. Differential regulation of apoliporotein B secretion from HepG2 cells by two HMG-CoA reductase inhibitors: atorvastatin and simvastatin[J].J LipidRes.1999; 40: 1078-1089.
    
    [33]Xu G, Pan LX, Li H, et al. Dietary cholesterol stimulates CYP7A1 in rats because farnesoid X receptor is not activated[J]. Am J Physiol Gastrointest Liver Physiol. 2004;286(5): G730-735.
    
    [34]Yang, T T. Koo, M W. Chinese green tea lowers cholesterol level through an increase in fecal lipid excretion[J]. Life Sci.2000; 66(5): 411 —423.
    
    [35]Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis [J]. Science. 1986; 232: 34-47.
    
    [36]Defesche JC, Schuurman EJ, Klaaijsen LN, et al.Silent exonic mutations in the low-density lipoprotein receptor gene that cause familial hypercholesterolemia by affecting mRNA splicing[J]. Clin Genet. 2008; 73(6): 573—578.
    
    [37]Cathcart M K. Regulation of superoxide anion production by NADPH oxides in monocytes/macrophages: contributions to atherosclerosis[J]. Arterioscler Thromb Vasc Biol.2004; 24(1):23-28.
    [1]Alessandri N,Piccioni MG,Isabelli V,et al.Morphological and functional changes of cardiovascular system in postmenopausal women[J].Eur Rev Med Pharmacol Sci.2007;11(2):107-117.
    [2]Albertazzi P,Purdie D.the nature and ultlity of the phytoestrogens:a review of the evidence[J].Maturitas.2002;42(3):173-185.
    [3]Crisafulli A,Altavilla D,Marini H,et al.Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women[J].Menopause.2005;12(2):186-192.
    [4]Altavilla D,Crisafulli A,Marini H,et al.Cardiovascular effects of the phytoestrogen genistein[J].Curr Med them Cardiovascular Hematological Agents.2004;2(2):178-196.
    [5]Rossouw J E,Anderson C L,Lacroix A Z,et al.Risks and benefits of estrogen plus progestin in healthy postmenopausal women principal results from the Women's Health Initiative randomized controlled trial[J].JAMA.2002;288(3):321-323.
    [6]Wu W H,Kang Y P.Wanc.N H,et al.Sesame ingestion affects sex homones antioxidant status and blood lipids in postmenopausul women[J].J Nutr.2006;136(5):1270-1275.
    [7]郑元元,杨京,陈迪华,等.木豆叶芪类提取物对雌激素缺乏性大鼠骨质丢失的影响.药学学报,2007;42(5):562-565.
    [8]王文蔚,朱红叶,余清,等.染色木黄酮对去卵巢大鼠血脂代谢的影响及抗氧化作用研究.浙江医学,2006;28(9):714-719.
    [9]余清,楼新法,王文蔚,等.大豆异黄酮对去势大鼠脂质过氧化及肝超微结构的影响.解剖学报.2007;38(5):601-605.
    [10]葛喜珍,田平芳,林强,等.大豆异黄酮对卵巢切除大鼠低密度脂蛋白受体(LDL-R)mRNA表达的影响.中药材.2006;29(4):349-351.
    [ll]Melhus G,Solberg LB,Dimmen S,et al.Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rats[J].Acta Orthop.2007;78(3):393-403.
    [12]Yao W,Tian XY,Chen J,et al.Rolipram,a phosphodiesterase 4 inhibitor,prevented cancellous and cortical bone loss by inhibiting endosteal bone resorption and maintaining the elevated periosteal bone formation in adult ovariectomized rats[J].J Musculoskelet Neuronal Interact.2007;7(2):119-130.
    [13]Saltiki K,Cimponeriu A,Lili K,et al.Severity of coronary artery disease in postmenopausal diabetic women.Hormones(Athens).2008;7(2):148-155.
    [14]Konukoglu D,Serin Q,Ercan M,et al.The relationship between plasma viscostity and cholesterol in postmenopausal women on hormone replacement therapy[J].Clin Hemorheol Microcirc.2000;22(3):223-228.
    [15]Mograno M M,Changw,Isatzenellenhogen BS,et al.An estrogen recepte elective eorepressor:Cloning and Characterization[J].Endocrinol.1998,98(1):96-98.
    [16]Levine,Keanky J F,VitaJ A.Cholesterol reduction in cardiovascular disease clinical benefits and possible mechanisms[J].N Engl J med.1995;322(10):512-521.
    [17]Wenger NK.The current state of hormonal prevention of coronary heart disease in menopausal women[J].Rev Esp Carrdiol.2003;56(1):1-8.
    [18]陆建建,许春平,曾波,等.绝经后女性性激素、血脂变化与冠心病的研究.中国老年学杂志.2006;26(4):453-454.
    [19]杨彬.绝经妇女的血脂变化及其意义.临床内科杂志.2004;19(S1):87-88.
    [20]韦建琪,杜敏,刘惠英.老年绝经后妇女血脂和雌激素与冠心病关系.兵团医学.2005;2:16-17.
    [21]Shlipakm G,Simon J A,Vittinghoff E,et al.Estrogen and progestin lipoprotein(a),and the risk of recurrentcoronary heart disease events after menopause[J].JAMA, 2002; 283(10): 1845-1852.
    
    [22]Writing group for the PEPI trial. Effect of homrone replacement therapy on endometrial histology in postmenopausal women[J].JAMA. 1996; 275(5): 370—375.
    
    [23]Glazia MG, Bowman MA. A review of the evidence for the use of phytoestrogen for traditional estrogen replacement therapy[J]. Arch Inter Med.2001; 9(16): 1161 —1171.
    
    [24]Gajdos C, Jordan V C. Selective estrogen receptor modulator as a new therapeutic drug group: concept to reality in a decad[J].Clin Breast Cancer. 2002; 36(2): 272-281.
    
    [25]Kreijkamp-Kaspers S, Kok L, Bots M L, et al. Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women: a cross-sectional study[J]. Atherosclerosis.2005; 178(1): 951-956.
    
    [26]Asgary S, Moshtaghian J, Naderi G, et al. Effects of dietary red clover on blood factors and cardiovascular fatty streak formation in hypercholesterolemic rabbits[J].Phytother Res. 2007; 21(8): 768-770.
    
    [27]Lucas EA, Lightfoot SA, Hammond LJ, et al. Flaxseed reduces plasma cholesterol and atherosclerotic lesion formation in ovariectomized Golden Syrian hamsters[J].Atherosclerosis. 2004; 173(2): 223—229.
    
    [28]Goss PE, Qi S, Cheung AM, et al. Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats[J]. Clin Cancer Res. 2004; 10(17): 5717—5723.
    
    [29]Armamento-Villareal R, Sheikh S, Nawaz A, et al.A new selective estrogen receptor modulator, CHF 4227.01, preserves bone mass and microarchitecture in ovariectomized rats[J].J Bone Miner Res. 2005; 20(12): 2178—2188.
    
    [30]Jazbutyte V, Hu K, Kruchten P, et al.Aging reduces the efficacy of estrogen substitution to attenuate cardiac hypertrophy in female spontaneously hypertensive rats[J]. Hypertension. 2006; 48(4): 579—586.
    [1]Fustr V.Badimon J.Chesebro J H.Atherothrombosis mechanisms and clinical therapeutic approaches[J].Vasc MeD.1998;3(3):211-223.
    [2]Yancey PG,Bortnick AE,Kellner-Weibel G,et al.Importance of different pathways of cellular cholesterol efflux[J].Arterioscler Thromb Vasc Biol.2003;23(5):712-719.
    [3]Brewer HB Jr.High-density lipoproteins:a new potential therapeutic target for the prevention of cardiovascular disease[J].Arterioscler Thromb Vasc Biol.2004;24(3):387-391.
    [4]Liu L,Bortnick AE,Nickel M,et al.Effects of apolipoprotein A-I on ATP-binding cassette transporter Al-mediated efflux of macrophage phospholipid and cholesterol:formation of nascent high density lipoprotein particles[J].J Biol Chem.2003;278(44):42976-42984.
    [5]赵战芝,杨永宗,王佐,等.肥大细胞改变THP-1巨噬细胞源性泡沫细胞胆固醇含量及抑制胆固醇流出.中国病理生理杂志.2007;23(8):1457-146.
    [6]Brundert M,Heeren J,Bahar-Bayansar M,et al.Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI[J].J Lipid Res.2006;47(11):2408-2241.
    [7]Kim WS,Rahmanto AS,Kamili A,et al.Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-beta peptide generation[J].J Biol Chem.2007:282(5):2851-2861.
    [8]Lin G R,Bornfeldt K,E.Cyclic AMP-specific phosphodiesterase 4 inhibitors promote ABCA1 expression and cholesterol effiux[J].Biochem Biophys Res Commun.2002;290(2):663-669.
    [9]Oliver WR Jr,Shenk JL,Snaith MR,et al.A selective peroxisome proliferators activated receptor delta agonist promotes reverse cholesterol transport[J].Proc Natl Acad Sci U SA.2001;98(9):5306-5311.
    [10]Van Dam MJ,de Groot E,Clee SM,et al.Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol effiux:an observational study[J].Lancet.2002;359(9300):37-42.
    [11]Srivastava RA.Estrogen-induced regulation of the ATP-binding cassette transporter A1(ABCA1) in mice:a possible mechanism of atheroprotection by estrogen[J].Mol Cell Biochem.2002;240(1-2):67-73.
    [12]Napolitano M,Blotta I,Montali A,et al.17beta-estradiol enhances the flux of cholesterol through the cholesteryl ester cycle in human macrophages[J].Biosci Rep.2001;21(5):637-652.
    [13]Guan J Z,Tamasawa N,Murakami H,et al.HMG-CoA reductase inhibitor,simvastatin improves reverse cholesterol transport in type 2 diabetic patients with hyperlipidemia[J].J Atheroscler Thromb.2008;15(1):20-25.
    [14]W6jcicka G,Jamroz-Wisniewska A,Horoszewicz K,et al.Liver X receptors (LXRs).Part Ⅰ:structure,function,regulation of activity,and role in lipid metabolism[J].Postepy Hig Med Dosw(Online).2007:61:736-759..
    [15]骆庆峰,孙兰,杜冠华.胆固醇逆向转运过程中新靶点及其药物的研究进展.中国药理学通报.2006;22(8):904-907.
    [16]Faulkner LE,Panagotopulos SE,Johnson JD,et al.An analysis of the role of a retroendocytosis pathway in ABCA1-mediated cholesterol effiux from macrophages[J].J Lipid Res.2008;49(6):1322-1332.
    [17]Tall AR.Cholesterol effiux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins[J].J Intern Med.2008;263(3):256-273.
    [18]Nofer JR,Remaley AT.Tangier disease:still more questions than answers[J].Cell Mol Life Sci.2005;62(19-20):2150-2160.
    [19]Lewis GF,Rader DJ.New insights into the regulation of HDL metabolism and reverse cholesterol transport[J].Circ Res.2005;96(12):1221-1232.
    [1]Siegel-Axel D,Daub K,Seizer P,et al.Platelet lipoprotein interplay:trigger of foam cell formation and driver of atherosclerosis[J].Cardiovasc Res.2008;78(1):8-7.
    [2]Takahashi K,Takeya M,Sakashita N.Multifunctional roles ofmacrophages in the development and progression of atherosclerosis in humans and experimental animals[J].Med Electron Microscopy,2002;35(4):179-203.
    [3]Maor I,Aviram M.Oxidized low density lipoprotein leads to macrophage accumulation of unesterified cholesterol as a result of lysosomal trapping of the lipoprotein hydrolyzed cholesteryl ester[J].J Lipid Res.1994;35(5):803-819.
    [4]Lange Y,Steck TL.The role of intracellular cholesterol transport in cholesterol homeostasis[J].Trends Cell Biol.1996;6(6):205-208.
    [5]Choudhury R P,Lee JM,Greaves D R.Mechanisms of disease:macrophage derived foam cells emerging as therapeutic targets in atherosclerosis[J].Nat Clin Pract CardiovascMed,2005;2(6):309-315.
    [6]Chan ES,Zhang H,Fernandez P,et al.Effect of cyclooxygenase inhibition on cholesterol efflux proteins and atheromatous foam cell transformation in THP-1 human macrophages:a possible mechanism for increased cardiovascular risk[J].Arthfitis Res Ther.2007;9(1):R4 doi:10.1186/ar2109.
    [7]Miike T,Shirahase H,Jino H,et al.Effects of an anti-oxidative ACAT inhibitor on apoptosis/necrosis and cholesterol accumulation under oxidative stress in THP-1cell-derived foam cells[J].Life Sci.2008;82(1-2):79-84.
    [8]何雪峰,李晓辉,李淑慧,等.三七总皂苷对小鼠巨噬细胞源性泡沫细胞形成的影响.中国药房.2007;18(30):2323-2325.
    [9]郑伟,周洁,陈娟,等.甲基莲心碱对RAW264.7巨噬细胞泡沫化的影响.医学分子生物学杂志.2005;2(3):170-174.
    [10]雷新军,马爱群,席雨涛,等.阻断Kv1.3和Kir2.1抑制人巨噬细胞源性泡沫细胞分化.中南大学学报(医学版).2006;31(4):493-498.
    [11]蒋佩,严鹏科,莫中成,等.促进细胞内胆固醇流出抑制单核细胞源性泡沫细胞凋亡.中国病理生理杂志.2005;21(6):1041-1045.
    [12]雷新军,马爱群,席雨涛,等.阻断MaxiK通道对人单核细胞源性巨噬细胞向泡沫细胞分化的抑制作用.细胞与分子免疫学杂志,2006;22(3):310-313.
    [13]覃丽,秦旭平,王佐,等.普伐他汀对泡沫细胞内胆固醇醋的影响及与小凹蛋白-1的关系.生理学报.2006;58(1):47-52.
    [14]Fogelman A M,Shechter I,Seager J,et al.Malondialdehyde Alteration of Low Density Lipoproteins Leads to Cholesteryl Ester Accumulation in Human Monocyte Macrophages[J].Proc Natl Acad Sci,1980;77(4):2214-2218.
    [15]Schaffner T, Taylor K, Bartucci E, et al.Arterial foam cells with distinctive immunomorphages [J]. Am J Pathol. 1980; 100 (1): 57—80.
    
    
    [16]Gerrity R G. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. [J]. Am J Pathol. 1981; 103 (2) : 181-190.
    
    [17]Ross. The pathogenesis of atherosclerosis: a perspective for the 1990s [J]. Nature,1993; 362 (6423) : 801-809.
    
    [18]Boyle J J. Macrophage activation in atherosclerosis : pathogenesis and pharmacology of plaque rupture[J]. Curr Vasc Pharmacol. 2005; 3(1): 63—68.
    
    [19]Itabe H, Takano T. Oxidized low density lipoprotein: the occurrence and metabolism in circulation and in foam cells [J]. J Atheroscler Thromb. 2000; 7(3):123-131.
    
    [20]Bobryshev, Y. V. Monocyte recruitment and foam cell formation in atherosclerosis[J]. Micron. 2006; 37 (3) : 208—222.
    
    [21]Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease[J]. N.Engl.J.Med.2005; 352 (16) : 1685-1695.
    
    [22]Cox BE, Griffin EE, Ullery JC, et al. Effects of cellular cholesterol loading on macrophage foam cell lysosome acidification[J]. J Lipid Res. 2007; 48(5): 1012—1021.
    
    [23]Baoutina A, Dean R T, Jessup W. Antioxidant properties of macrophages toward low-density lipoprotein [J]. Trends Cardiovasc Med. 2001; 11(1): 1—7.
    
    [24]Brown A J, Mander EL, Gelissen IC, et al. Cholesterol and oxysterol metabolism and subcellular distribution in macrophage foam cells. Accumulation of oxidized esters in lysosomes [J]. J Lipid Res.2000; 41(2): 226-237.
    [1]Grand-Peret T,Bouillot A,Perrot A,et al.SCAP ligands are potent new lipid -lowering drugs[J].Nat Med.2001;7(12):1332-1338.
    [2]骆庆峰,孙兰,杜冠华.胆固醇逆向转运过程中新靶点及其药物的研究进展.中国药理学通报.2006;22(8):904-907.
    [3]Rigotti A,Miettinen H E,Krieger M.The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues[J].Endocr Rev.2003;24(3):357-387.
    [4]Nguyen P,Leray V,Diez M,et al.Liver lipid metabolism[J].J Anim Physiol Anita Nutr(Berl).2008;92(3):272-283.
    [5]B(o|¨)hm M,Werner C,Jakobsen A,et al.Treating to protect:current cardiovascular treatment approaches and remaining needs[J].Medscape J Med.2008;10 Supph S3.
    [6]Angelin B.Regulation of hepatic cholesterol metabolism in man[J].Ann Med.1991;23(2):177-180.
    [7]Rudling MJ,Reihner E,Einarsson K,et al.Low density lipoprotein receptor binding activity in human tissues:quantitative importance of hepatic receptors and evidence for regulation of their expression in vivo[J].Proc Natl Acad Sci U S A.1990;87(9):3469-3473.
    [8]Jeon H,Blacklow SC.Structure and physiologic function of the low-density lipoprotein receptor[J].Annu Rev Biochem.2005;74:535-562.
    [9]Tserentsoodol N,Sztein J,Campos M,et al.Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process[J].Mol Vis.2006;12:1306-1318.
    [10]Hannah J S,Yamane K,Berlin E,et al.In vitro regulation of low density tipoprotein receptor interaction by fatty acids[J].Metabolism,1995;44(11):1428-1434.
    [11]Benn M,Nordestoaard B G,Jensen J S,et al.Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the LDL receptor[J]. J Biol Chem, 2005; 280(22): 21052-21060.
    
    [12]Azhar, S., and E. Reaven. Scavenger receptor class BI and selective cholesteryl ester uptake: partners in the regulation of steroidogenesis[J]. Mol Cell Endocrinol.2002; 195 (1-2) : 1-26.
    
    [13]Zhar. S, S. Leers-Sucheta, Reaven. Cholesterol uptake in adrenal and gonadal tissues: the SR-BI and 'selective' pathway connection[J]. Front. Biosci. 2003; 8(Suppl.): 998-1029.
    
    [14]Silver, D. L., and A. R. Tall. The cellular biology of scavenger receptor class B type I[J]. Curr. Opin. Lipidol. 2001; 12 (5) : 497-504.
    
    [15]Reaven E, Cortez Y, Leers-Sucheta S, et al. Dimerization of the scavenger receptor class B type I: formation, function, and localization in diverse cells and tissues[J]. J Lipid Res. 2004; 45(3): 513-528.
    
    [16] Zhang Y, Ahmed A M, Mc Farlanc N, et al. Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary derived cells by protein kinase signaling pathways[J]. J Lipid Res. 2007; 48(2): 405-416.
    [1]郑元元,杨京,陈迪华,等.木豆叶提取物对人的类成骨细胞TE85成骨功能和体外破骨细胞分化的影响。药学学报.2007;42(4):386-391.
    [2]郑元元,杨京,陈迪华,等.木豆叶芪类提取物对雌激素缺乏性大鼠骨质丢失的影响.药学学报.2007;42(5):562-565.
    [3]孙兰,汪青,刘景生.雌激素促进人的类成骨细胞TE85成骨作用的受体机制.药学学报.1999;34(8):561-564.
    [4]Rosemary Steinmetz,Peter C.M.Young,Andrea Caperell-Grant,et al.Novel estrogenic action of the pesticide residue β-hexachlorocyclohexane in human breast cancer cells[J].Cancer research.1996;56:5403-5409.
    [5]郑光,孙运光,戴旭峰,等.竞争性受体结合试验检测农药拟雌激素样作用.环境与职业医学.2003;20(6):403-405.
    [6]黄毅娜,程薇波,徐培渝,等.双酚A和对-壬基酚雌激素受体的竞争性结合.中国公共卫生,2004;20(5):559-561.
    [7]闫平,李煌元,张文昌,等.镉对雌激素与雌激素受体结合能力影响的实验研究.毒理学杂志,2005:19(1):41-42.
    [8]Chen H,Xiao J,Hu G,et al.Estrogenicity of organophosphorus and pyrethroid pesticides[J].J Toxicol Environ Health A.2002;65(19):1419-1435.
    [9]Pal R,Chaturvedi R,Kamboj KK,et al.Estrogen receptors in rat bone:their interaction with estrogen receptor modulators[J].Endocr Res.2001;27(3):283-291.
    [10]Klann A,Levy G,Lutz I,et al.Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor(Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells[J].Environ Res.2005;97(3):274-281.
    [11]Kim HS,Han SY,Yoo SD,et al.Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays[J].J Toxicol Sci.2001;26(3):111-118)
    [12]Shao W L,Myles Brown.Advances in estrogen receptor biology prospects for improvements in targeted breast cancer therapy[J].Breast Cancer Res.2004;6(1):39-52.
    [13]Sirtori CR,Arnoldi A,Johnson SK.Phytoestrogens:end of a tale?[J].Ann Med.2005;37(6):423-438.
    [14]Turner JV,Agatonovic-Kustrin S,Glass BD.Molecular aspects of phytoestrogen selective binding at estrogen receptors[J].J Pharm Sci.2007;96(8):1879-1885.
    [15]Moon YJ,Wang X,Morris ME.Dietary flavonoids:effects on xenobiotic and carcinogen metabolism[J]. Toxicol In Vitro. 2006; 20(2): 187—210.
    
    [16]Belcher SM, Zsarnovszky A. Estrogenic action in the brain: estroge, phytoestrogen,and rapid intracellular sigaling mechanisms[J]. Jpharmac Experi Thera.2001; 299(2):408-415.
    
    [17]Bovee TF, Helsdingen RJ, Rietjens IM, et al. Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types[J]. J Steroid Biochem Mol Biol.2004; 91(3): 99-109.
    
    [18]Mueller SO, Simon S, Chae K, et al. Phytoestrogens and their human metabolites show distinct agonistic and antagonistic properties on estrogen receptor a (ERa) and ERβ in human cells[J]. Toxicol Sci. 2004; 80 (1): 14—25.
    
    [19]Ricketts ML, Moore DD, Banz WJ, et al. Molecular mechanisms of action of the soy isoflavones includes activation of promiscuous nuclear receptors. A review[J]. J Nutr Biochem. 2005; 16(6): 321-330.
    
    [20]Chindewa R, Lapanantasin S, Sanvarinda Y, et al.Pueraria mirifica, phytoestrogen induced change in synaptophysin expression via estrogen receptor in rat hippocampal neuron[J].J MedAssoc Thai. 2008; 91(2): 208-214.
    
    [21]Stettner M, Kaulfuss S, Burfeind P, et al.The relevance of estrogen receptor-beta expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment[J]. Mol Cancer Ther. 2007; 6(10):2626-2633.
    
    [22]Kavlock R J. Overview of endocrine disruptor research activity in the United States [J].Chemosphere.1999; 39(8): 1227-1236.
    [1]Nachman R L,Jaffe E A.Endothelial cell culture:beginnings of modem vascular biology[J].J Clin Invest.2004;114(8):1037-1040.
    [2]Loscalzo J,Voetsch B,Liao R,et al.Genetic determinants of vascular oxidant stress and endothelial dysfunction[J].Congest Heart Fail.2005;11(2):73-79.
    [3]Ross R.The pathogenesis:a perspective for the 1990s[J].Nature.1993;362(6423):801-809.
    [4]Takahashi H,Hara K.Expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) in human preeclamptic placenta:possible implications in the process of trophoblast apoptosis[J].Placenta.2005;26:226-233.
    [5]Ince A,Sch(u|¨)tze N,Hendrich C,et al.Effect of polyhexanide and gentamycin on human osteoblasts and endothelial cells[J].Swiss Med Wkly.2007:137(9-10):139-145.
    [6]Maas R,Schulze F,Baumert J,et al.Asymmetric dimethylarginine,smoking,and risk of coronary heart disease in apparently healthy men:prospective analysis from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg study and experimental data[J].Clin Chem.2007;53(4):693-701.
    [7]Alexander H,Dalpke,Reiner Thomssen,et al.Oxidative injury to endothelial cells due to Epstein-Barr virus induced autoantibodies against manganese superoxide diamutase[J].J med virol.2003;71(3):408-416.
    [8]Lewin MH,Arthur JR,Riemersma RA,et al.Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides[J].Biochim Biophys Acta.2002;1593(1):85-92.
    [9]杜建玲,安利佳,孙长凯,等.SelS高表达保护人脐静脉内皮细胞免于H_2O_2诱导的细胞损伤.生物化学与生物物理进展.2007;34(4):425-430.
    [10]何煜舟,丁美萍.木犀草素对H_2O_2氧化损伤的血管内皮细胞的影响.中国病理生理杂志.2007;23(7):1285-1288.
    [11]许晶兰,王孝铭,王东霞.复方丹参滴丸对过氧化氢损伤的人脐静脉血管内皮细胞的保护作用.中国病理生理杂志.2006;22(5):929-932.
    [12]张健,魏欣冰,丁华,等.卡维地洛对过氧化氢致血管内皮细胞氧化应激损伤的保护作用.中国药理学通报.2006;22(5):620-624.
    [13]Dominik B,Pete C.Endothelial function from vascular biology to clinical applications[J].Am J Cardiol.2002;90(10C):40L-48L.
    [14]Sch(a|¨)er A,Bauersachs J.Endothelial dysfunction,impaired endogenous platelet inhibition and platelet activation in diabetes and atherosclerosis[J].Curr Vasc Pharmacol.2008:6(1):52-60.
    [15]Callow AD.Endothelial dysfunction in atherosclerosis[J].Vascul Phamacol.2002;38(5):257-258.
    [16]Schulz S,Birkenmeier G,Schacdarsurencin U,et al.Role of LDL receptor related protein(LRP) in coronary atherosclerosis[J].Int J Cardiol.2003;92(2-3);137-144.
    [17]Warren MC,Bump EA,Mcdciros D,et al.Oxidative stress-induced apoptosis of endothelial cells[J].Free Radic Res.2000;29(6):537-547.
    [18]Lopez-Farre A,Casado S.Heart failure,redox altemalions and endothelial dysfunction[J].Hype rtension. 2001; 38(6): 1400—1405.
    
    [19]Rossing L, Hofflnann J, Hugel B. Vitamin C inhibits endothelial cell apoptosis in congestive heart failure[J]. Circulation. 2001; 104(18): 2182—2187.
    
    [20]Schulz E, Jansen T, Wenzel P, et al. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension[J]. Antioxid Redox Signal. 2008;10(6): 1115-1126.
    
    [21]Annu K M, Zilmer M, Fellstrom B. Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: Impact on cardiovascular disease[J]. Kidney Int Suppl.2003; 84(6): S50-53.
    
    [22]Cathcart M K. Regulation of superoxide anion production by NADPH oxides in monocytes/macrophages: contributions to atherosclerosis[J]. Arterioscler Thromb Vasc Biol. 2004; 24(1):23-28.
    
    [23]Bian K, Doursout MF, Murad F. Vascular system: role of nitric oxide in cardiovascular diseases[J]. J Clin Hypertens (Greenwich). 2008; 10(4): 304—310.
    
    [24]Woodman OL. Modulation of vasoconstriction by endothelium derived nitric oxide: The influence of vascular disease[J]. Clin Exp Phamacol Physiol. 1995; 22(9):585-593.
    
    [25]Canipan RC, Wang BY, Buitrago R, et al.Regression or progression dependency on vascular nitric oxidc.[J]. Atheroscler Thromb Vasc Biol. 1999; 16( 1): 44—50.
    
    [26]Kim YM, Kim TH, Scol DW, et al. Nitric oxide suppression of apoptosis occurs in association with an inhibition of bcl-2 cleavage and cytochrome C release[J]. J Biol Chcm. 1998; 273(47): 31437-31441.
    
    [27]Kassab A, Leban N, Ferchichi S, et al.Oxidant stress and cardiovascular absolute risk in Tunisian type 2 diabetes[J]. Ann Biol Clin (Paris). 2008; 66(2): 151 — 156.
    
    [28]Gordon LA, Morrison EY, McGrowder DA, et al. Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes[J]. BMC Complement Altern Med.2008 ; 8(1): 21. doi: 10.1186/1472-6882-8-21.
    
    [29]张均田,张庆柱、张永详主编.神经药理学.北京:人民卫生出版社, 2008, 4:233-251.
    [1]Glass CK,Witztum J L.Atherosclerosis the road ahead[J].J Cell.2001;104(4):503-516.
    [2]Chen Pin,XU Xiang-jin.Anti-proliferative effects of compound Danshen dripping pill on rabbit aortic smooth muscle cells during the insulin resistance state[J].Chin J TCMW M Crit Care.2007;14(5):313-316.
    [3]徐志红,陆国平,吴春芳.同型半胱氨酸对大鼠血管平滑肌细胞增殖及胶原生成的影响.中国组织工程研究与临床康复.2007;11(2):226-229. 细胞增殖.中国心血管病研究杂志.2007;5(3):224-226.
    [5]GUO Tao,LIU Mini-yan,SUI Yin,et al.Effects of serum contained Xinshu oral liquid on rat aorta smooth muscle cell proliferation and rabbit platelet aggregation in vitro[J].Chin Pharm J.2005;40(19) 1466-1469.
    [6]Florence Gizard,Dennis Bruemmer.Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-γ:Therapeutic Implications for Cardiovascular Diseases.PPAR Res.2008:doi:10.1155/2008/429123.
    [7]Noma K,Rikitake Y,Oyama N,et al.ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury[J].J Clin Invest.2008;118(5):1632-1644.
    [8]黄广勇,卢才义.动脉粥样硬化血管重塑的认识与研究进展.心血管病学进展.2005;26(6):589-592.
    [9]Davis MG,Hagen PO.Pathobiology of intimal hyperplasia[J].Br J Surg.1994;81:1254-1259.
    [10]Ross R.Atherosclerosis:an inflammatory disease[J].N Eng J Med.1999;340:115-126.
    [1]Sarah M.Mense,Tom K.Hei,Ramesh K.Ganju,et al.Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action[J]. Environ Health Perspect. 2008;116(4): 426-433.
    
    [2] Messina M, McCaskill-Stevens W, Lampe JW. Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings[J]. J Natl Cancer Inst.2006: 98(18): 1275-1284.
    
    [3]Deroo BJ, Korach KS.Estrogen receptors and human disease[J]. J Clin Invest 2006;116(3): 561-570.
    
    [4]Adlercreutz H, Heinonen SM, Penalvo-Garcia J. Phytoestrogens, cancer and coronary heart disease[J]. Biofactors.2004; 22(1-4): 229—236.
    
    [5]Zhang G, Qin L, Sheng H, et al. Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition[J]. Bone. 2007; 40(3): 685—692.
    
    [6]Mak P, Leung YK, Tang WY,et al.A pigenin suppresses cancer cell growth through ERbeta[J].Neoplasia.2006; 8(11): 896-904.
    
    [7]Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism[J]. Toxicol In Vitro. 2006; 20(2): 187—210.
    
    [8]Kris-Etherton PM, Hecker KD, Bonanome A, et al, Bioactive compounds in foods:Their role in the prevention of cardiovascular disease and cancer[J]. Am J Med, 2002;113(9B): 71S-88S.
    
    [9]DixonRA. Phytoestrogens[J]. Annu Rev Plant Biol.2004; 55: 225—261.
    
    [10]Magee PJ, Rowland IR. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer[J]. Br J Nutr.2004; 91(4): 513—531.
    
    [11] Allred CD, Allred KF, Ju YH, et al. Soy diets containing varying amounts of genistein stimulate growth of estrogen dependent (MCF-7) tumors in a dose-dependent manner[J]. Cancer Res.2001; 61(13): 5045—5050.
    
    [12]Allred CD, Twaddle NC, Allred KF, et al. Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized BALB/c mice[J]. J Agric Food Chem.2005; 53(22): 8542—8550.
    [13] Webb AL, McCullough ML. Dietary lignans: potential role in cancer prevention[J].Nutr Cancer.2005; 51(2): 117-131.
    
    [14]Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health[J]. Exp Biol Med (Maywood).2005; 230(3): 155-170.
    
    [15]Adlercreutz H. Phyto-estrogens and cancer[J]. The lancet Oncol.2002; 3: 364—373.
    
    [16] Pennalvo JL, Haajanen K M, Bolting N, et el.Quantification of lignans in food using isotope dilution gas chromatography/mass spectrometry[J]. J Agric Food Chem.2005; 53(24): 9342-9347.
    
    [17]Milder I E, Arts I C, Putts B, et al. Lignan contents of dutch plant foods: A database including Larciresinol, pinoresinol, secoisolariciresinol and mataresinol[J]. Br J Nutr.2005; 93(3): 393-402.
    
    [18] Sirtori CR, Arnoldi A, Johnson SK. Phytoestrogens: end of a tale?[J]. Ann Med.2005; 37(6): 423-438.
    
    [19] Stob M, Baldwin RS, Tuite J, et al. Isolation of an anabolic uterotrophic compound from corn infected with Gibbezella Zeae[J]. Nature. 1962; 196: 1318.
    
    [20]Limer J L, Speirs V. Phytoestrogens and breast cancer chemoprevention[J]. Breast Cancer Res.2004; 6(3): 119-127.
    
    [21]Peeters PH, Keinan-Boker L, vander Schouw YT, et al. Phytoestrogens and breast cancer risk. Review of the epidemiological evidence[J]. Breast Cancer Res Treat.2003; 77(2): 171-183.
    
    [22]Harper CE, Patel BB, Wang J, et al. Resveratrol suppresses prostate cancer progression in transgenic mice[J]. Carcinogenesis. 2007; 28(9): 1946— 1953.
    
    [23]Dai Q, Franke AA, Yu H, et al. Urinary phytoestrogen excretion and breast cancer riskrevaluating potential effect modifiers endogenous estrogens and anthropometrics [J]. Cancer Epidemiol Biomarkers Prev. 2003; 12(6): 497—502.
    
    [24]Boccardo F, Puntoni M, Guglielmini P, et al.Enterolactone as an risk factor for breast cancer: a review of the published evidence[J]. Clin Chim Acta.2006; 365(1-2): 58-67.
    
    [25]Verheus M, van Gils CH, Keinan-Boker L, et al. Plasma phytoestrogens and subsequent breast cancer risk[J]. J Clin Oncol.2007; 25(6): 648-655.
    
    [26] Whitsett TG Jr, lamartinlere CA. Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat[J]. Expert Rev Anticancer Ther.2006; 6(12): 1699-1706.
    
    [27]Cotterchio M, Boucher BA, KreigerN, et al. Dietary phytoestrogen intake-lignans and isoflavones-and breast cancer risk (Canada) [J]. Cancer Causes Control. 2008;19(3): 259-272.
    
    [28]Keinan-Boker L, van Der Schouw YT, Grobbee DE, et al. Dietary phytoestrogens and breast cancer risk[J].Am J Clin Nutr. 2004; 79(2): 282—288.
    
    [29] Waite KA, Sinden MR, Eng C. Phytoestrogen exposure elevates PTEN levels[J].Hum Mol Genet. 2005; 14(11): 1457-1463.
    
    [30] Sharon A, Sylvia M, Carl O, et al. Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model[J]. Cancer Res. 2005; 65(8): 3396—3403.
    
    [3 l]Cherdshewasart W, Panriansaen R, Picha P. Pretreatment with phytoestrogen-rich plant decreases breast tumor incidence and exhibits lower profile of mammary ERalpha and ERbeta[J]. Maturitas. 2007; 58(2): 174—181.
    
    [32] Zeming Jin, Ruth S. Soy isoflavones increase latency of spontaneous mammary tumors in mice[J].J Nutr.2002; 132(10): 3186—3190.
    
    [33] Mishra P, Kale RK, Kar A. Chemoprevention of mammary tumorigenesis and chemomodulation of the antioxidative enzymes and peroxidative damage in prepubertal Sprague Dawley rats by Biochanin A[J]. Mol Cell Biochem. 2008; 312(1-2): 1—9.
    
    [34] Coral A, Michelle S, Wayne A, et al.Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate[J].J Nutr.2002; 132(3): 552—558.
    
    [35] Stettner M, Kaulfuss S, Burfeind P, et al. The relevance of estrogen receptor-beta expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment[J]. Mol Cancer Ther. 2007; 6(10):2626-2633.
    
    [36] Kurahashi N, Iwasaki M, Sasazuki S, et al. Japan Public Health Center-Based Prospective Study Group, Soy product and isoflavone consumption in relation to prostate cancer in Japanese men[J]. Cancer Epidemiol Biomarkers Prev. 2007; 16(3):538-545.
    
    [37] Barqawi A, Thompson IM, Crawford ED. Prostate cancer chemoprevention: an overview of United States trials[J]. J Urol. 2004; 171(2Pt 2): S5—8.
    
    [38]Vij U, Kumar A. Phyto-oestrogens and prostatic growth[J]. Natl Med J India. 2004;17(1): 22-26.
    
    [39]Morrissey C, Bektic J, Spengler B, et al. Phytoestrogens derived from Belamcanda chinensis have an antiproliferative effect on prostate cancer cells in vitro[J]. J Urol.2004; 172(6 Pt 1): 2426-2433.
    
    [40]Mentor-Marcel R, Lamartiniere C A, Ctoum I E, et al. Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice(TRAMP) [J]. Cancer Res.2001; 61(18): 6777-6782.
    
    [41]Landstom M, Zhang J X, Hallmans G, et al. Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats[J].Prostate. 1998; 36(3): 151-161.
    
    [42]Gallo D, Giacomelli S, Cantelmo F, et al. Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy[J]. Breast Cancer Res Treat.2001; 69(2): 153—164.
    
    [43] Schabath MB, Hernandez LM, Wu X, et al. Dietary phytoestrogens and lung cancer risk[J]. JAMA. 2005; 294(12): 1493-1504.
    
    [44] Abarzua S, Szewczyk M, Gailus S, et al. Effects of phytoestrogen extracts from Linum usitatissimum on the Jeg3 human trophoblast tumour cell line[J]. Anticancer Res.2007; 27(4A): 2053-2058.
    
    [45]Ying C, Hsu J T, Hung H C, et al. Growth and cell cycle regulation by isoflavones in human breast carcinoma cells[J].Reprod Nutr Dev.2002; 42(1): 55—64.
    
    [46]Sunil U, Madhavi N, Sveenivasa R, et al. Differential sensitivity of normal and malignant breast epithelial cells to genistein is partly mediated by p21~(WAF1)[J]. Clin Cancer Res.2001; 7(6): 1782-1789.
    
    [47]Choi Y H, Lee W H, Park K Y, et al. p53 Independent induction of p21(WAF1CIP1), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells[J].Jpn J Cancer Res. 2000; 91(2): 164-173.
    
    [48]Ana M P, Luis E V, Marcela A P, et al. Dietary isoflavones affect sex hormone-binding globulin levels in post-menopausal women[J]. J Clin Endorcrinol Metab.2000; 85(8): 2797-2800.
    
    [49]Xia X, Alison M D, Kerry E W, et al. Soy consumption altars endogenous estrogen metabolism in postmenopausal women[J]. Cancer Epidemiol Biomarkers Prev. 2000;9(8): 781-786.
    
    [50]Brooks J D, Thompson L U. Mammalian lignans and genistein decress the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF27 cells[J]. Steriod Biochem Mol Biol.2005; 94(5): 461—467.
    
    [51]Abraham SK, Schupp N, Schmid U, et al. Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid[J]. Mol Nutr Food Res. 2007; 51(7): 880—887.
    
    [52]Bianco N R, Chaplin L J, Montano M M. Differential induction of quinine reductase by phytoestrogens and protential against oestrogen induced DNA damage[J].Biochem J.2005; 385(1): 279-286.
    
    [53]Xu J W, Ikeda K, Yamori Y. Genistein inhibits expressions of NADPH oxidase p22phox and antiotensin type 1 receptor in aortic cells from stroke-prone spontaneously hypertensive rats[J]. Hypertens Res.2004; 27(9): 675—683.
    
    [54]Duncan R E, El-Sohemy A, Archer M C. Dietary factors and the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for breast cancer and development[J]. Mol Nutr Food Res.2005; 49(2): 93—100.
    [55]Dorien W V, Alina V, Laura J, et al. The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies[J]. Cancer Epidemiol Biomarkers Prev.2005; 14(1): 195-203.
    
    [56]Rickard S E, Yuan Y Y, Thompson L U. Plasma insulin-like growth factor I levels in rats are reduced by dietary supplementation of flaxseed or its lignan secoisolariciresinol diglycoside[J]. Cancer Lett. 2000; 161(1): 47~55.
    
    [57]Zhou J R, Mukherjee P, Gugger E T, et al. Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis[J]. Cancer Res.1998; 58(22): 5231-5238.
    
    [58]Dabrosin C, ChenJ, Wang L, et al. Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts[J].Cancer Lett. 2002; 185(1): 31-37.
    
    [59]Markovits J, Linassier C, Fosse P, et al. Inbitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II[J]. Cancer Res. 1989; 49(18):5111-5117.
    
    [60] Castro A F, Aotenberg G A. Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein[J]. Biochem Pharmacol. 1997;53(1): 89-93.
    
    [61]Zhang S, Morris M E. Effects of the flavonoid biochanin A, morin, phloretin, and silymarin on P-goycoprotein-mediated transport[J]. Pharmacol Exp Ther. 2003;304(3): 1258-1267.
    
    [62]Wietzke J A, Ward E C, Schneider J, et al. Regulation of the human vitamin D3 receptor promoter in breast cancer cells is mediated through SP1 sites[J]. Mol Cell Endocrinol.2005; 230(1-2): 59-68.
    
    [63]Wietzke J A, Welsh J. Phytoestrogen regulation of a vitamin D3 receptor promoter and 1,25-dihydroxyvitamin D3 actions in human breast cancer cells[J]. Steroid Biochem Mol Biol.2003; 84(223): 149-157.
    
    [64] Alessandri N, Piccioni MG, Isabelli V, et al. Morphological and functional changes of cardiovascular system in postmenopausal women[J]. Eur Rev Med Pharmacol Sci.2007; 11(2): 107-117.
    
    [65]Crisafulli A, AltavillaD, Marini H, et al. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women[J]. Menopause. 2005; 12 (2):186-192
    
    [66] Lobo R A. Benefits and risks of estrogen replacement therapy [J]. Am J Obstet Gynecol.1995; 173(3Pt2): 982-989.
    
    [67] Wu W H, Kang Y P, Wane. N H, et al. Sesame ingestion affects sex homones antioxidant status and blood lipids in postmenopausul women[J]. J Nutr. 2006; 136(5):1270-1275.
    
    [68]Lichtenstein A H, Jalbert S M, Adlercreutz H, et al. Lipoprotein response to diets high in soy or animal protein with and without isofluvones in moderately hypercholesterolemic subjects[J]. Arterioseler Thromb Vasc Biol. 2002;22(l 1): 1852—1858.
    
    [69] Sanders T A, Dean T S, Grainger D, et al. Moderate intakes of intact soy protein rich in isoflavones compared with ethanol-extraced soy protein increase HDL but do not influence transfoming growth factor beta(I) concentrations and hemostatic risk factors for coronary heart disease in healthy subjects[J]. Am J Clin Nmr. 2002; 76(2):373-377.
    
    [70] Jenkins D J. Effect of soy protein foods on low-density lipoprotein oxidation and ex vivo sex hormone receptor activity controlled crossover trial[J]. Metabolism.2000;49(4): 537—543.
    
    [71]Kreijkamp-Kaspers S, Kok L, Bots M L, et al. Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women: a cross-sectional study[J]. Atherosclerosis.2005; 178(1): 95—100
    
    [72]Clarkson T B, Anthony m S, Morgan T M. Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens [J]. J Clin Endocrinol Metab.2001; 86(1): 41 —47.
    [73]Goodman G, Kritz S. Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women[J]. J Nutr. 2001; 134(4):1202-1206.
    
    [74] Scheiber M D, Liu J H, Subbiah ML et al. Dietary inclusion of whole soy food sresults in significant reductions in clinical risk factors for osteoporosis and cardiovsascular disease in normal postmenopausal women[J]. Menopause.2001; 8(5):384-392.
    
    [75]Nagata C, Takatsuka N, Kurisu Y, et al. Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women[J].J Nutr. 1998: 128(2): 209-213.
    
    [76]Goodma-Gruen D, Krilz-Silverstein D. Usual Dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women[J]. J Nutr.2001; 131(4): 1202-1206.
    
    [77] Squadrito F, Altavilla D, MarabiLo N, et al. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations. endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women [J]. Atherosclerosis. 2002; 163(2):339-347.
    
    [78]Uesugi T, Fukui Y, Yamori Y. Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal Japanese women: a four-week study[J]. J Am Coll Nutr. 2002; 21(2): 97—102.
    
    [79]Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women[J]. J Clin Endocrinol Metab. 2002; 87(1): 118-121.
    
    [80] Albertazzi P, Purdie DW. The nature and utility of the phytoestrogens: a review of the evidence[J]. Maturitas.2002; 42(3): 173—185.
    
    [81]Branca F, Lorenzetti S. Health effects of phytoestrogens[J]. Forum Nutr.2005;57(8): 100-111.
    
    [82]Asgary S, Moshtaghian J, Naderi G, et al. Effects of dietary red clover on blood factors and cardiovascular fatty streak formation in hypercholesterolemic rabbits[J].Phytother Res. 2007; 21(8): 768—770.
    
    [83] Rachon D, Vortherms T, Seidlova-Wuttke D, et al.Effects of dietary equol on body weight gain, intra-abdominal fat accumulation, plasma lipids, and glucose tolerance in ovariectomized Sprague-Dawley rats[J]. Menopause. 2007; 14(5): 925—932.
    
    [84]Ruhlen RL, Howdeshell KL, Mao J, et al.Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the"fetal estrogenization syndrome"and obesity in CD-1 mice[J]. Environ Health Perspect. 2008; 116(3): 322-328.
    
    [85]Borradaile NM, de Dreu LE, Wilcox LJ. Soy phytoestrogens, genistein and daidzein decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms[J].Biochem J.2002; 366(Pt2): 531-539.
    
    [86]Cederroth CR, Vinciguerra M, K(?)hne F, et al. A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice[J]. Environ Health Perspect. 2007;115(10): 1467-1473.
    
    [87] Adams MR, Golden DL, Register TC, et al. The atheroprotective effect of dietary soy isoflavones in apolipoprotein E-/-mice requires the presence of estrogen receptor-alpha [J]. Arterioscler Thromb Vase Biol. 2002; 22(11): 1859—1864
    
    [88]Kuiper GG, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta[J].Endocrinology. 1997; 138(3): 863-870.
    
    [89] Vina J, Sastre J, Pallardo FV, et al.Modulation of longevity-associated genes by estrogens or phytoestrogens. Biol Chem. 2008; 389(3): 273—277.
    
    [90] Kaamanen M, Adlercreutz H, Jauh iainen M. et al. Accumntulation of genistein and lipophilic genistein derivatives in lipoproteins during incubation with human plasma in vitro[J]. Biochim Biophys Acta. 2003; 1631(2): 147-152.
    
    [91]Wiseman H, O' Reillv JD, Adlercreutz H, et al. Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane concentration and increase resistance of low-density lipoprotein to oxidation in humans [J]. Am J Clin Nutr. 2000; 72(2): 395— 400.
    
    [92]Exner M, Hermann M, Holbauer R. et al. Genistein, prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein[J]. Free Radic Res. 2001; 34(1): 101-112.
    
    [93]Kitts D D, Yuan Y V, Wijewickreme AN, et al. Antioxidant activity of the flaxseed lignan secoieobuiciresinol diglycoeide and its mammalian lignan metabolites enterodiol and enterolactone[J]. Mol Cell Biochem.1999; 202(1-2): 91-100.
    
    [94]Praead K. Antioxidant activity of secoisolaricireainol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone [J]. Int J Angiol. 2000;9(4): 220-225.
    
    [95]Niemeyer H B, Metzler M. Differences in the antioxidant activity of plant and mammalian lignans [J].J Food Eng. 2003; 56 (2): 255—232.
    
    [96]Pool-Zobel B L, Adlercreutx H, Glei M, et al. Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells [J].Carcinogenesis.2000; 21(6): 1247—1252.
    
    [97]Aoki H, Otaka Y, Igarashi K, et al. Soy protein reduces paraquat-induced oxidative stress in rats[J]. J Nutr. 2002; 132(8): 2258-2262.
    
    [98]Hashimoto M, Miyao M, Akishita M, et al. Effects of long-term and reduced-dose hormone replacemen therapy on endothelial function and intima-media thickness in postmenopausal women[J]. Menopause.2002; 9(1): 58—64.
    
    [99]Chan YH, Lau KK, Yiu KH, et al. Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden[J]. Am J Clin Nutr. 2007; 86(4): 938-945.
    
    [100] Steinberg F M, Guthrie N L, Villablanca A C, et al. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women [J].Am J Clin Nutr, 2003; 78(1):123-130.
    
    [ 101]Garcia-martinez M C, Hermenegildo C, Tarin J J, et al. Phytoestrogens increase the capacity of serum to stimulate prostacyclin release in human endothelial cells [J].Acta Obstet Gynecol Scand.2003; 82(8): 705—710.
    
    [102]Karmsetty M R, Klinger J R, Hill N S. Phytoestrogens restore nitric oxide-mediated relaxation in isolated pulmonary arteries from chronically hypoxicrats[J].J Pharmacol Exp Ther.2001; 297(3): 968-974.
    
    [103]Figtree G A, Griffiths H, Lu Y Q, et al. Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism[J]. J Am Coll Cardiol.2000;35(7): 1977-1985.
    
    [104] Crisafulli A, Altavilla D, Marini H, et al. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women[J]. Menopause. 2005; 12(2):186-192.
    
    [105]Cullen JP, Morrow D, Jin Y, et al. Resveratrol, a polyphenolic phytostilbene,inhibits endothelial monocyte chemotactic protein-1 synthesis and secretion[J]. J Vasc Res. 2007; 44(1): 75-84.
    
    [106]Williams J K, Anthony M S, Herrington D M. Interactive effects of soy protein and estradiol on coronary artery reactivity in atherosclerotic ovariectomized monkeys [J].Menopause.2001; 8(5): 307-313.
    
    [107]Ling S, Dai A, Williams MR, et al. The isoflavone metabolite cistetrahydrodai-dzein inhibits ERK-1 activation and proliferation in human vascular smooth muscle cells[J]. J Cardiovasc Pharmacol. 2004; 43(5): 622—628.
    
    [108]Si H, Liu D. Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats[J].J Nutr. 2008; 138(2): 297—304.
    
    [109]Duan J, Xu H, Dai S, et al. Phytoestrogen alpha-zearalanol inhibits homocysteine induced endothelin-1 expression and oxidative stress in human umbilical vein endothelial cells[J]. Atherosclerosis.2008; 197(2): 549—555.
    
    [110]Cruz M N, Luksha L, Logman H, et al. Acute responses to phytoestrogens in small arteries from men with coronary heart disease[J]. Am J Physiol Heart Circ Physiol. 2006; 290(5): 1969-1975.
    
    [111]Li H F, Wang L D, Qu S Y, et al. Phytoestrogen genistein decreases contractile responses of aortic artery in vitro and arterial blood pressure in vivo[J]. Acta Pharmacol Sin.2004; 25(3): 313-318.
    
    [112]Chao HH, Juan SH, Liu JC, et al. Resveratrol inhibits angiotensin II-induced endothelin-1 gene expression and subsequent proliferation in rat aortic smooth muscle cells[J].Eur J Pharmacol.2005; 515(1-3): 1—9.
    
    [113]Woodman OL, Missen MA, Boujaoude M. Daidzein and 17 beta-estradiol enhance nitric oxide synthase activity associated with an increase in calmodulin and a decrease in caveolin-l[J].J Cardiovasc Pharmacol. 2004; 44(2): 155—163.
    
    [114]Nakaya Y, Mawatari K, Takahashi A, et al.The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways[J]. J Med Invest. 2007; 54(3-4): 381—384.
    
    [115] Vera R, Jimenez R, Lodi F, et al.Genistein restores caveolin-1 and AT-1 receptor expression and vascular function in large vessels of ovariectomized hypertensive rats[J].Menopause. 2007; 14(5): 933-940.
    
    [116] Polini N, Rauschemberger MB, Mendiberri J, et al.Effect of genistein and raloxifene on vascular dependent platelet aggregation[J]. Mol Cell Endocrinol. 2007;267(1-2): 55-62.
    
    [ 117]Gardner JD, Brower GL, Voloshenyuk TG, et al.Cardioprotection in female rats subjected to chronic volume overload: synergistic interaction of estrogen and phytoestrogens[J]. Am JPhysiol Heart Circ Physiol. 2008; 294(1): H198—204.
    
    [118]Liu M, Yanagihara N, Toyohira Y, et al. Dual effects of daidzein, a soy isoflavone, on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells[J]. Endocrinology. 2007; 148(11): 5348—5354.
    
    [119] Atteritano M, Marini H, Minutoli L, et al. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study[J]. J Clin Endocrinol Metab.2007; 92(8): 3068-3075.
    
    [120]Tissier R, Waintraub X, Couvreur N, et al. Pharmacological postconditioning with the phytoestrogen genistein[J]. J Mol Cell Cardiol. 2007; 42(1): 79—87.
    
    [121] File S E, Duffy R, Wiseman H. Improved memory and frontal lobe function in post-menopausal women after 3 month's treatment with soy supplements[J].Eur J Neuropsycho pharmacol. 2002 ; 12(7): S406—411.
    
    [122]Chindewa R,Lapanantasin S,Sanvarinda Y,et al.Pueraria mirifica, phytoestrogen-induced change in synaptophysin expression via estrogen receptor in rat hippocampal neuron[J]. J Med Assoc Thai. 2008; 91(2): 208-214.
    
    [123]Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Dietary phytoestrogen intake and cognitive function in older women[J]. J Gerontol A Biol Sci Med Sci. 2007; 62(5):556-562.
    
    [124] Kritz-Silverstein D, Von M(?)hlen D, Barrett-Connor E, et al. Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study[J]. Menopause. 2003; 10(3): 196-202
    
    [125] Park D, Huang T, Frishman WH. Phytoestrogens as cardioprotectiv agents[J].Cardiol Rev.2005; 13(1): 13-17.
    
    [126]Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized, controlledtrial[J]. Obstet Gynecol Surv, 2005;60(6): 41-43.
    
    [127] Xu X, Zhang Z. Effects of puerarin on synaptic structural modification in hippocampus of ovariectomized mice[J]. Planta Med. 2007; 73(10): 1047—1053.
    [128] Shi C, XuXW, Forster EL, etal. Possible role of mitochondrial dysfunction in central neurodegeneration of ovariectomized rats[J]. Cell Biochem Funct. 2008; 26(2):172—178.
    
    [129]Shir Y, Campbell JN, Raja SN, et al.The correlation between dietary soy phytoestrogens and neuropathic pain behavior in rats after partial denervation[J]. Anesth Analg.2002; 94(2): 421-426.
    
    [130]Dong YL, Zuo PP, Li Q, et al. Protective effects of phytoestrogen alpha-zearalanol on beta amyloid25-35 induced oxidative damage in cultured rat hippocampal neurons[J].Endocrine. 2007; 32(2): 206-211.
    
    [131]Chandeying V, Lamlertkittikul S.Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women[J].J Med Assoc Thai. 2007; 90(7): 1274-1280.
    
    [132]Upmalis D H, Lobo R, Bradley L, et al. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind,randomized, placebo-controlled study[J]. Menopause, 2000; 7(4): 236—242.
    
    [133] Cassidy A, Albertazzi P, Lise Nielsen I, et al. Critical review of health effects of soyabean phytoestrogens in post-menopausal women[J]. Proc Nutr Soc.2006; 65(1):76-92.
    
    [134]Lethaby AE, Brown J, Marjoribanks J, et al Phytoestrogens for vasomotor menopausal symptoms[J]. Cochrane Database Syst Rev. 2007; 17(4): CD001395.
    
    [135]Chilibeck PD, Cornish SM.Effect of estrogenic compounds (estrogen or phytoestrogens) combined with exercise on bone and muscle mass in older individuals[J]. Appl Physiol Nutr Metab. 2008; 33(1): 200-212.
    
    [136]Morabito N , Crisafulli A, Vergara C , et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study[J]. J Bone Miner Res. 2002; 17(10):1904-1912.
    
    [137]Alekel D L, Germain A S, Peterson C T, et al. Isoflavone-rich soy protein isolated attaenuates bone loss in the lumbar spine of perimenopausal women[J]. Am J Clin Nutr.2000; 72(3): 844-852.
    
    [138]Marini H, Minutoli L, Polito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial[J]. Ann Intern Med.2007; 146(12): 839-847.
    
    [139]Uchiyama S, Yamaguchi M. Genistein and zinc synergistically enhance gene expression and mineralization in osteoblastic MC3T3-E1 cells[J]. Int J Mol Med. 2007;19(2): 213-220.
    
    [140]Kanno S, Hirano S, Kayama F. Effects of phytoestrogen and environmental estrogens on osteoblastic differentiation in MC3T3-Elcells[J]. Toxicology. 2004;196(12): 137-145
    
    [141]Gao Y H, Yamaguchi M. Suppressive effect of genistein on rat bone osteoclast:involvement of protein kinase inhibition and protein tyrosine phosphatase activation[J].Int J Mol Med. 2000; 5(3): 261-267.
    
    [142]Rassi C M, Lieberherr M, Chaumaz G, et al. Down-regulation of osteoclast differentiation by daidzein via caspase3[J]. J Bone Miner Res. 2002; 17(4): 630—638.
    
    [143]Dai Z, Li Y, Quarles LD, et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation[J]. Phytomedicine. 2007; 14(12): 806—814.
    
    [144] Aneja R, Upadhyaya G, Prakash S, et al. Ameliorating effect of phytoestrogens on CC14-induced oxidative stress in the livers of male Wistar rats[J]. Artif Cells Blood Substit Immobil Biotechnol.2005; 33(2): 201-213.
    
    [145]Wang H, Li H, Moore LB, et al. The phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane x receptor[J]. Mol Endocrinol. 2008;22(4): 838-857.
    
    [146]]Yalniz M, Bahcecioglu IH, Kuzu N, et al. Preventive role of genistein in an experimental non-alcoholic steato hepatitis model[J]. J Gastroenterol Hepatol. 2007;22(11): 2009-2014.
    
    [147]Usr(?)n Y, Engin-Ust(?)n Y, Ovayolu A, et al. The effect of resveratrol on prevention of the development of postoperative adhesions in a rat model[J]. Gynecol Endocrinol. 2007; 23(9): 518-522.
    
    [148]Harada N, Okajima K, Arai M, et al.Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in mice and in humans with alopecia[J]. Growth Horm IGF Res. 2007; 17(5): 408—415.
    
    [149]Lin CC, Chen JL, Ko WC.Relaxation of isolated guinea pig trachea by genistein via inhibition of phosphodiesterase[J]. Planta Med. 2007; 73(4):323—329.
    
    [150]Lau WS, Chan RY, Guo DA, et al. Ginsenoside Rg1 exerts estrogen-like activities via ligand-independent activation of ERalpha pathway[J]. J Steroid Biochem Mol Biol.2008; 108(1-2): 64—71.
    
    [151] GreschikH, Flaig, I RenaudP. et al. Structural basis for the deactivation of the estrogen-related receptor by diethylstilbestrol or 4-hydroxytamoxifen and determinants ofselectivity[J].J Biol Chem, 2004; 279(32): 33639-33646.
    
    [152]Luo. I, Sladek R, Carrier. et al. Reduced fat mass in mice lacking orphan nuclear receptor estrogen recelated receptor [J].Mol Cell Biol.2003; 23(22): 7947—7956.
    
    [153]Chen ZT, Zhou P, He L, et al. QSAR of estrogen of bisphenol A with 3D vector of atomic property correlation [J]. Chinese J Struct Chem, 2007; 26(81): 988—994.
    
    [154]Shaaban AM, Jarvis C, Moot F, et al. Prognostic significance of estrogen receptor beta in epithelial hyperplasia of usual type with known outcome [J]. Am J Surg Pathol.2005; 29(12): 1593-1599.
    
    [155] Sakaguchi H, Fujimoto I, Bao LH, et al. Quantitative analysis of estrogen recept-proteins in rat ovary [J].J Steroid Biochem Mole Bid. 2005; 94(7): 83—91.
    
    [156]Fixemer T, Remberger K, Bonkhof H. Differential expression of the estrogen receptorbeta (ERbeta) in human prostate trssue, and in primary, and recurrent prostatic adenocarcinoma [J]. Prostate,2003; 54(2): 79—87.
    
    [157]Medeiros R, Vasconcelos A, Costa S.et al. Steroid hormone genotypes ARStul and ER325 are linked to the progression cancer [J]. Cancer Genet Cytogenet. 2003; 141(2):91—96.
    
    [158]Somponpun S I, Sladek C D. Osmotic regulation of estrogen receptor beta in rat vasopressin and oxytocin neurons [J].J Neurosci. 2003; 23(1): 4261 —4269.
    
    [159] Schoenau E. Bone mass increase in puberty: what makes it happen[J]. Horm Res. 2006: 65(S2): s2-10.
    
    [160]Sims NA, Dupont S, KrustA, et al. Deletion of estrogen receptors reveals a regulatory role for estrogen receptor beta in bone remodeling in females but not in males[J].Bone.2002; 30: 18-25.
    
    [161] ]Zhang ZL, QinY, Huang QR, et al. Association of estrogen receptor alpha and vitamin D receptor genotypes with therapeutic responses to calcium in postmenopausal Chinese women[J]. Acta Pharmacologica Sinica. 2004; 25( 12): 1690-1697.
    
    [162]Kalita K, Szymczak S, Kaczmarek L. Non-nuclear estrogen receptor αandβin the hippocampus of male and female rats[J]. Hippocampus. 2005; 15 (1): 404—412.
    
    [163] (Paraskevi, Moutsatsou.The spectrum of phytoestrogens in nature: our knowledge is expanding[J]. Hormones 2007; 6(3): 173—193.
    
    [164]Matthews J, Gustafsson JA. Estrogen signaling: a subtle balance between ERa and ERβ[J].Mol Interv 2003; 3 (5) : 281-292.
    
    [165]Wolters M, Hahn A. Soy isoflavones-a therapy for menopausal symptoms? [J].Wien Med Wochenschr.2004; 154 (13-14): 334-341.
    
    [166]Lu Q, Ebling H, Mittler J, et al. MAP kinase mediates growth factor-induced nuclear translocation of oestrogen receptor alpha[J]. FEBS lett.2002; 516 (1-3) : 1 —8.
    
    [167]Ring A, Dowsett M. Mechanisms of tamoxifen resistance[J]. Endocr Relat Cancer.2004; 11 (4) : 643-658.
    
    [168] Lamlertkittikul S, Chandeying V. Efficacy and safety of Pueraria mirifica (Kwao Kruea Khao) for the treatment of vasomotor symptoms in perim-enopausal women:Phase II Study[J].J Med Assoc Thai.2004; 87 (1): 33—40.
    
    [169]Ullmann U, Metzner J, Frank T. Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers[J].Adv Ther.2005; 22 (1): 65-78.
    
    [170]Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient[J] .Postgrad Med J.2005; 81(10): 266-267.
    
    [171] Menzel VA, Hinsch E, Hagele W, et al. Effect of genistein on acrosome reaction and zona pellucida binding independent of protein tyrosine kinase inhibition in bull[J].Asian JAndrol.2007; 9(5): 650-658.
    
    [172]Glover A, Assinder SJ. Acute exposure of adult male rats to dietary phytoestrogens reduces fecundity and alters epididymal steroid hormone receptor expression[J].J Endocrinol.2006; 189 (3): 565-573.
    
    [173]Giampietro PG, Bruno G, Furcolo G, et al.Soy protein formulas in children:no hormonal effects in long-term feeding[J]. J Pediatr Endocrinol Metab.2004; 17 (2):191-196.
    
    [174] Strom BL, Schinnar R, Zieglar EE, et al. Exposure to soybased formula in infancy and endocrinological and reproductive outcomes in young adulthood[J]. JAMA.2001;286 (7): 807-814.
    
    [175]Pan L, Xia X, Feng Y, et al.Exposure to the phytoestrogen daidzein attenuates apomorphine-induced penile erection concomitant with plasma testosterone level reduction in dose- and time-related manner in adult rats[J]. Urology. 2007; 70(3): 613—617.
    
    [176]Balk JL, Whiteside DA, Naus G, et al. A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium[J].J Soc Gynecol Investig.2002; 9(4): 238-242.
    
    [177] Crisafulli A, Marini H, Bitto A, et al. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT-and placebo-controlled study[J]. Menopause.2004; 11 (4): 400—404.
    
    [178]Unfer V, Casini ML, Costabile L, et al. Endometrial effects of long-term treatment with phytoestrogens:a randomized, double-blind, placebo-controlled study[J].Fertil Steril.2004; 82 (1): 145-148.
    
    [179]Kurzer MS.Phytoestrogen supplement use by women[J].J Nutr.2003; 133:S1983-S1986.
    [180]Dimitrakakis C, Gosselink L, Gaki V, et al.Phytoestrogen supplementation:a case report of male breast cancer[J].Eur J Cancer Prev.2004; 13 (6): 481-484.
    
    [181]Park D, Huang T, Frishman WH.Phytoestrogens as cardioprotective agents[J].Cardiol Rev.2005; 13 (1): 13-17.
    
    [182] Branca F, Lorenzetti S. Health effects of phytoestrogens[J].Forum Nutr.2005; 57:100-111.
    
    [183]Piersen CE.Phytoestrogens in botanical dietary supplements:implications for cancer[J].Integr Cancer Then 2003; 2 (2): 120—138.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址：北京市海淀区学院路29号 邮编：100083

电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700