几种生理调节剂对去卵巢大鼠骨质疏松症防治机理的研究
|
摘要
骨质疏松症是一种影响人类身体健康的重要疾病。某些畜禽骨质疏松症发病率也很高，如笼养蛋鸡。研究表明，虽然大豆黄酮、金雀异黄酮、依普拉芬等生理调节剂均有一定的防治骨质疏松症的作用，但它们的确切防治效果及作用机理不明显，文献报道不一。半胱胺是一种生长抑素的耗竭剂。它可提高生长激素的水平，促进生长，但它有无防治骨质疏松症作用，仍不详。本研究的目的是通过骨质疏松动物模型，研究几种大豆异黄酮和半胱胺对防治骨质疏松症效果及其作用机理，为防治人及笼养蛋鸡骨质疏松症提供依据。实验分两个部分。
1．IP98和Ge对防治去卵巢大鼠骨质疏松症比较研究
目的：探讨IP98和金雀异黄酮(Ge)对去势大鼠骨代谢的影响，以比较它们的疗效。
方法：选用70只3月龄大鼠随机分为假手术组(Sham)，去势对照组(OVX)，IP98治疗组(OVX+IP98)，金雀异黄酮治疗组(OVX+Ge)四组。Sham组、OVX组饲喂基础日粮；OVX+IP98组在基础日粮中添加100 mg·kg~(-1)的IP98，OVX+Ge组在基础日粮中添加50mg·kg~(-1)的金雀异黄酮。实验持续3个月。每个10天测定体重，实验结束时，分别测定骨密度、血清AKP、StrACP、BGP、E_2等。
结果：与假手术组比较，去势对照组、IP98治疗组、金雀异黄酮治疗组体重均显著增加(P＜0.01)，但去势各组间差异不显著(P＞0.05)；IP98治疗组血清AKP、BGP、StrACP水平比去势对照组显著降低(P＜0.05)，也低于假手术组，但Ge治疗组血清AKP、StrACP比IP98有增高的趋势(P＞0.05)，而BGP则显著高于OVX+IP98组(P＜0.05)；假手术组雌激素水平显著高于去势对照组、IP98治疗组、Ge组(P＜0.01)。IP98治疗组雌激素水平与去势对照组比较差异不显著(P＞0.05)，Ge治疗组则差异显著(P＜0.05)，也高于IP98治疗组。各组骨密度(BMD)差异不显
著(P>0 .05)。
结论:本试验每公斤大鼠饲料中分别添加IP98 IO0mg和金雀异黄酮somg均有
改善骨代谢标志物的作用，证实两者对防止去卵巢诱发的骨丢失均有效，但IP98
作用更明显。
2.大豆黄酮和半耽胺对去卵巢大鼠骨质琉松症的防治作用
方法:120只3月龄雌性SD大鼠，进行双侧卵巢切除术和假手术，将其随机
分为假手术组(sham)、去卵巢对照组(OVX)、治疗组(OVX+CS300 mg/kg)及
预防组(OvX+大豆黄酮40Om留kg+半胧胺300m留kg)。术后3个月屠宰半数大
鼠，余数在另3个月后屠宰。每两周称重一次，取大鼠椎骨及股骨用于骨矿密度
(BMD)测定，收集血样分析血钙、血磷、碱性磷酸酶(AKP)、骨钙素(BGP)、
雌激素( EZ)、生长激素(GH)和降钙素(CT)。
结果:大鼠体重随其周龄的增长而增加，半肤胺治疗组增重最快，半肤胺+大
豆黄酮组体重低于去势对照组，假手术组增重最慢:半胧胺治疗组AKP、BGP水平
除显著高于假手术组和去势对照组(P<0.05，尸<0.01)，也显著高于大豆黄酮组。但
大豆黄酮组AKP、BGP水平均低于或显著低于去势对照组(尸<0.05);试验中、后
期，半肤胺组和半胧胺+大豆黄酮组血钙水平均显著低于假手术组和去势对照组
(尸<0.05)，各组间血磷水平无显著变化:降钙素水平在试验中期仅半胧胺组高于其
他各组，试验后期各组间无显著性差异;在试验中、后期，假手术组雌激素水平极
显著高于去势对照组和治疗组(P<0.01);试验后期半肤胺治疗组GH水平显著高于
假手术组和去势对照组(尸<0 .01)，但半肤胺+大豆黄酮组GH水平却显著低于半胧
胺(尸<0.05);试验中期各去卵巢组右侧股骨骨密度明显下降(P<0.0l)，但试验后期
由于受体重的影响，各组之间变化不大(尸为.05)。
结论:大鼠去双侧卵巢后3个月可建立骨质疏松症动物模型。骨代谢标志物显
示，长期使用大豆黄酮对阻止骨丢失有效，半肤胺效果不甚明显。
Osteoporosis was an important disease affecting human health. It was showed that the physiologic regulators such as diadzein, genistein, iproflavone and cysteamine took a role in prevention and treatment of osteoporosis. But it has not been clearly known about effectiveness and mechanism of diadzein, genistein, iproflavone and whether or not action of cysteamine in prevention and treatment of osteoporosis. The aid of this experiment is that effect of several isoflavones and cysteamine on prevention and treatment of osteoporosis were investigated with in the Ovariectomized Rats. The parts of this experiment were shown as follows:
1. Studies on comparison between Genistein (Ge) and Ipriflavone
(IP98) for treatment of osteoporosis in the OVX rats.
Objective: To determine effect of IP98 and Ge on bone metabolism and compare two isoflavones in curative effect of osteoporosis in OVX rats and
Method : Seventy female Sprague-Dawley rats were allocated randomly into four groups, that is, sham(Sham), ovariectomized controll(OVX), ipriflavone(IP98)treatment and genistein(Ge)treatment groups. Ovariectomies were performed in the OVX, OVX-Gn(I) and OVX-IP98(II) groups. Animals in the SHAM group were subjected to sham operation. Shame and OVX groups were fed with basic diets. IP98 and Ge groups were fed with basic diets supplemented with Ipriflavone(IP98) 100 mg.kg-1 and 1 Genistein(Ge) of 50mg.kg-1 , respectively. The body weight were determined in 10 day interval. All rats were killed 3 months after surgery, their body and comb weight were both examined in the test. Three months Blood alkaline phosphtase (AKP), estradiol(E2), osteocalcin (BGP), strACP were examined.
Results: Compared to the Sham group, body weight were increased evidently in the OVX, OVX-Gn, OVX-IP98 groups(P<0.01). The difference among the three groups was not signifcant. Comb weight in the sham group was infinitely higher than other groups(P<0.01); Compared to OVX group, the values of AKP, BGP and strACP in serum in OVX-IP98 group was decreased(P<0.05) and sham group, but values of AKP, BGP and strACP were tendency to increase in OVX-Gn group compared to OVX-IP98 group(p<0.05); The values of E2 in serum in Sham group was distinctly higher than those in OVX, OVX-IP98, OVX-Ge group(P<0.01). Compared to OVX, levels of E2 in OVX-Ge group were decreased markedly (P<0.01), However, difference of the bone mineral density (BMD) was not appeared among those groups(.P>0.05).
Conclusions: Ipriflavone(IP98)100 mg.kg-1 Genistein(Ge) 50mg.kg-1 is effective in preventing bone loss induced and inhibit bone resorption effectly by osteoporosis in the ovariectomized rats. But IP98 was more curative effect than Ge.
2. The roles of Daidzein and Cysteamine on the treatment of
Osteoporosis in the OVX rats.
Method: In 120 female Sprague-Dawley rats aged 3 month, either bilateral ovariectomy (OVX) or sham surgery was performed. All rats were randomly subjected to control group(sham), ovariectomized controll group(OVX), OVX-cysteamine treatment group(300 mg/kg BW cysteamine, CS)(CS group) and OVX-daidzein-cysteamine treatment group (400 mg/kg BW daidzein, Da and 300 mg/kg BW CS)(Da+CS group) .Half of the rats were killed 3 months after surgery, and another half rats were killed 6 months after surgery. Their body weight were measured once in two weeks, and bones were taken from the vertebrae and femur for the examination of bone mineral density(BMD). Blood were collected to analyze for blood calcium, blood phosphorus, alkaline phosphtase (AKP), osteocalcin (BGP), estrogen (E2), growth hormone (GH), calcitonin (CT).
Results: The body weight of all rats were increased with aging(week age). Among them, the weight of CS group increased quickest, CS+Da group was lower than OVX group, and Sham group last; The levels of AKP, BGP in Cs group higher than Sham, OVX and Da groups significantIy(,P<0.05, P<0.01). The values of Ca in CS, CS+Da groups lower than sham and OVX groups significantly(P<0.05), and values of P in all
groups were not significant(P<0.05) in mediu
1．IP98和Ge对防治去卵巢大鼠骨质疏松症比较研究
目的：探讨IP98和金雀异黄酮(Ge)对去势大鼠骨代谢的影响，以比较它们的疗效。
方法：选用70只3月龄大鼠随机分为假手术组(Sham)，去势对照组(OVX)，IP98治疗组(OVX+IP98)，金雀异黄酮治疗组(OVX+Ge)四组。Sham组、OVX组饲喂基础日粮；OVX+IP98组在基础日粮中添加100 mg·kg~(-1)的IP98，OVX+Ge组在基础日粮中添加50mg·kg~(-1)的金雀异黄酮。实验持续3个月。每个10天测定体重，实验结束时，分别测定骨密度、血清AKP、StrACP、BGP、E_2等。
结果：与假手术组比较，去势对照组、IP98治疗组、金雀异黄酮治疗组体重均显著增加(P＜0.01)，但去势各组间差异不显著(P＞0.05)；IP98治疗组血清AKP、BGP、StrACP水平比去势对照组显著降低(P＜0.05)，也低于假手术组，但Ge治疗组血清AKP、StrACP比IP98有增高的趋势(P＞0.05)，而BGP则显著高于OVX+IP98组(P＜0.05)；假手术组雌激素水平显著高于去势对照组、IP98治疗组、Ge组(P＜0.01)。IP98治疗组雌激素水平与去势对照组比较差异不显著(P＞0.05)，Ge治疗组则差异显著(P＜0.05)，也高于IP98治疗组。各组骨密度(BMD)差异不显
著(P>0 .05)。
结论:本试验每公斤大鼠饲料中分别添加IP98 IO0mg和金雀异黄酮somg均有
改善骨代谢标志物的作用，证实两者对防止去卵巢诱发的骨丢失均有效，但IP98
作用更明显。
2.大豆黄酮和半耽胺对去卵巢大鼠骨质琉松症的防治作用
方法:120只3月龄雌性SD大鼠，进行双侧卵巢切除术和假手术，将其随机
分为假手术组(sham)、去卵巢对照组(OVX)、治疗组(OVX+CS300 mg/kg)及
预防组(OvX+大豆黄酮40Om留kg+半胧胺300m留kg)。术后3个月屠宰半数大
鼠，余数在另3个月后屠宰。每两周称重一次，取大鼠椎骨及股骨用于骨矿密度
(BMD)测定，收集血样分析血钙、血磷、碱性磷酸酶(AKP)、骨钙素(BGP)、
雌激素( EZ)、生长激素(GH)和降钙素(CT)。
结果:大鼠体重随其周龄的增长而增加，半肤胺治疗组增重最快，半肤胺+大
豆黄酮组体重低于去势对照组，假手术组增重最慢:半胧胺治疗组AKP、BGP水平
除显著高于假手术组和去势对照组(P<0.05，尸<0.01)，也显著高于大豆黄酮组。但
大豆黄酮组AKP、BGP水平均低于或显著低于去势对照组(尸<0.05);试验中、后
期，半肤胺组和半胧胺+大豆黄酮组血钙水平均显著低于假手术组和去势对照组
(尸<0.05)，各组间血磷水平无显著变化:降钙素水平在试验中期仅半胧胺组高于其
他各组，试验后期各组间无显著性差异;在试验中、后期，假手术组雌激素水平极
显著高于去势对照组和治疗组(P<0.01);试验后期半肤胺治疗组GH水平显著高于
假手术组和去势对照组(尸<0 .01)，但半肤胺+大豆黄酮组GH水平却显著低于半胧
胺(尸<0.05);试验中期各去卵巢组右侧股骨骨密度明显下降(P<0.0l)，但试验后期
由于受体重的影响，各组之间变化不大(尸为.05)。
结论:大鼠去双侧卵巢后3个月可建立骨质疏松症动物模型。骨代谢标志物显
示，长期使用大豆黄酮对阻止骨丢失有效，半肤胺效果不甚明显。
Osteoporosis was an important disease affecting human health. It was showed that the physiologic regulators such as diadzein, genistein, iproflavone and cysteamine took a role in prevention and treatment of osteoporosis. But it has not been clearly known about effectiveness and mechanism of diadzein, genistein, iproflavone and whether or not action of cysteamine in prevention and treatment of osteoporosis. The aid of this experiment is that effect of several isoflavones and cysteamine on prevention and treatment of osteoporosis were investigated with in the Ovariectomized Rats. The parts of this experiment were shown as follows:
1. Studies on comparison between Genistein (Ge) and Ipriflavone
(IP98) for treatment of osteoporosis in the OVX rats.
Objective: To determine effect of IP98 and Ge on bone metabolism and compare two isoflavones in curative effect of osteoporosis in OVX rats and
Method : Seventy female Sprague-Dawley rats were allocated randomly into four groups, that is, sham(Sham), ovariectomized controll(OVX), ipriflavone(IP98)treatment and genistein(Ge)treatment groups. Ovariectomies were performed in the OVX, OVX-Gn(I) and OVX-IP98(II) groups. Animals in the SHAM group were subjected to sham operation. Shame and OVX groups were fed with basic diets. IP98 and Ge groups were fed with basic diets supplemented with Ipriflavone(IP98) 100 mg.kg-1 and 1 Genistein(Ge) of 50mg.kg-1 , respectively. The body weight were determined in 10 day interval. All rats were killed 3 months after surgery, their body and comb weight were both examined in the test. Three months Blood alkaline phosphtase (AKP), estradiol(E2), osteocalcin (BGP), strACP were examined.
Results: Compared to the Sham group, body weight were increased evidently in the OVX, OVX-Gn, OVX-IP98 groups(P<0.01). The difference among the three groups was not signifcant. Comb weight in the sham group was infinitely higher than other groups(P<0.01); Compared to OVX group, the values of AKP, BGP and strACP in serum in OVX-IP98 group was decreased(P<0.05) and sham group, but values of AKP, BGP and strACP were tendency to increase in OVX-Gn group compared to OVX-IP98 group(p<0.05); The values of E2 in serum in Sham group was distinctly higher than those in OVX, OVX-IP98, OVX-Ge group(P<0.01). Compared to OVX, levels of E2 in OVX-Ge group were decreased markedly (P<0.01), However, difference of the bone mineral density (BMD) was not appeared among those groups(.P>0.05).
Conclusions: Ipriflavone(IP98)100 mg.kg-1 Genistein(Ge) 50mg.kg-1 is effective in preventing bone loss induced and inhibit bone resorption effectly by osteoporosis in the ovariectomized rats. But IP98 was more curative effect than Ge.
2. The roles of Daidzein and Cysteamine on the treatment of
Osteoporosis in the OVX rats.
Method: In 120 female Sprague-Dawley rats aged 3 month, either bilateral ovariectomy (OVX) or sham surgery was performed. All rats were randomly subjected to control group(sham), ovariectomized controll group(OVX), OVX-cysteamine treatment group(300 mg/kg BW cysteamine, CS)(CS group) and OVX-daidzein-cysteamine treatment group (400 mg/kg BW daidzein, Da and 300 mg/kg BW CS)(Da+CS group) .Half of the rats were killed 3 months after surgery, and another half rats were killed 6 months after surgery. Their body weight were measured once in two weeks, and bones were taken from the vertebrae and femur for the examination of bone mineral density(BMD). Blood were collected to analyze for blood calcium, blood phosphorus, alkaline phosphtase (AKP), osteocalcin (BGP), estrogen (E2), growth hormone (GH), calcitonin (CT).
Results: The body weight of all rats were increased with aging(week age). Among them, the weight of CS group increased quickest, CS+Da group was lower than OVX group, and Sham group last; The levels of AKP, BGP in Cs group higher than Sham, OVX and Da groups significantIy(,P<0.05, P<0.01). The values of Ca in CS, CS+Da groups lower than sham and OVX groups significantly(P<0.05), and values of P in all
groups were not significant(P<0.05) in mediu
引文
1．刘忠厚，潘子昂，王石麟．原发型骨质疏松症诊断标准的探讨．中国骨质疏松杂志，1997，3(1)：1-15
2．奚德华．猪骨软骨病关节软骨显微、超微结构变化及其相关细胞因子表达的研究．南京农业大学硕士论文，2003，9-11
3．金世鑫，汪耀，沈志卫．骨质疏松综合征：骨组织学和临床的联系(三)．中国骨质疏松杂志，1997，3(2)：62-65
4．于世凤．破骨细胞与骨吸收．中国骨质疏松杂志，1997，3(2)：72-74
5. Cheven B A A, Visser J W W, Nijuweide P J. In vitro osteoclast generation from different bone marrow fractions, including a highly enriched hemopoietic stem cell population. Nature, 1986,321:79-81
6．姜宏卫，程浩，董砚虎．骨形成调控机制研究进展．Foreigh Medical Sciences·Section of Pathophysiology and clinical Medicine. 2002,22(3):222-225
7. Zeng Ying, Mo Xinmin, Hong Jing. Experimental study on the role of calcium
phosphorus and calcium regulation hormone in the postmenopausal osteoporosis rats. 中国中医骨伤科杂志, 2001, 9 (5): 25-27
8. Horowitz Mc. Cytokines and estrogen in bone: anti-osteoporotic effects. Science, 1993, 260: 626.
9. McDonnell. D P, Norris J D. Analysis of the molecular pharmacology of estrogen receptor agonists and antagonists provides insights into the mechanism of action of estrogen in bone. Osteoporosis, 1997, Suppl 1:S29
10. Claude D. Arnaud, Sarah D. Sanchez. Calcium and Phosphorus. Present Knowledge in Nutrition. 1998,4:238-247
11. Wu Bo, Xu Bin, Huang Tianyou, et al. Changes of bone metabolism and the effects of estrogen treatment in ovariectomized rats. Chinese Pharmacological Bulletin, 1997,13(2):163-166
12. Liu Guangyao, Liu Fengyang. Use of calcitonin to treat osteoporosis in OVX rats. Chinese Journal of Osteoporosis, 1997, (3):15-17
13. An Shengjun, Li Tao, Li En. Effect of kidney-tonifying herbs on ovary function and bone mass in postmenopausal women. Chinese Journal of Osteoporosis, 2000, 6(2):55-59
14. Li Liang, Chen Huaiqing, He Changming, et al. Bone histomorphometry and bone mineral density changes in ovariectomized goats at regular intervals. Chinese Journal of Osteoporosis, 2000,6(2):10-12
15．乔伟伟，许兰文．骨质疏松症大鼠模型．上海试验动物科学，1997，17(3)：174-176
16. Anthony W, Norman. Vitamine D Present Knowledge in Nutrition. 1998,4:116-122
17．薛延．骨质疏松症诊断与治疗指南．北京：科学出版社，1999，432-454
18. Couch JR .Cage Layer Fatigue. Feed Age ,1995(5): 55-57
19. Ornoy A, Goodwin D, Noff D, and Edelstein S. 24,25-dihydroxyvitamin D is a metabolite of Vitamin Dessential for bone formation. Nature, 1978,276:517-519
20. Schwarta Z, Schlader DL, Swain LD, et al. Direct effect of 1,25-dihydroxyvitamin D_3 on growth zone chondrocyte membrane alkaline phosphatase and phospholipase-A_2 Specific activities. Endocrinology, 1988, 123:2878-2884
21. Markes SC Jr, Popoff SN. Bone cellbiology: The regulation of development, structure and function in skeleton. American Journal of Anatomy, 1988,183:1-44
22. Whitehead CC. Bone Biology and Skeletal Discorders in Poultry. Carfax Company, Oxfordor-shire , England, 1992, 182-280
23．韩正康，毛鑫智等编．家禽生理学．江苏科技出版社．1986，117
24．刘忠厚．骨质疏松学．北京：科学出版社，1998，109
25. Shugbrue P J, Dorsa D M. Estrogen modulates the growth-associated protein GAP-43 (neuromodulin) mRNA in the rat preoptic area and basal hypothalamus. Neuroendocrinology, 1993, 57(3):439-447
26. Mayer M, Rosin F. Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol. Am J Physiol, 1975,229:138
27．姜振玲．雌性激素影响大鼠生长激素结合蛋白水平．生理科学进展，1994，25(3)：222
28. Lindsay R, Hart D M, Aitken J M, et al. Lone term prevention of postmenopausal osteoporosis by estrogen. Lancert, 1976,1:1038
29．姜晓洪．雌激素抗骨质疏松的研究现状．医师进修杂志，2002，25(4)：55-56
30．孙兰，汪青，刘景生．雌激素促进人的类成骨细胞TE-85成骨作用的受体机制．药学学报，1999，34(8)：561-564
31．赵燕灵，朱传英，丁桂芝等．原发性骨质疏松症的发病机理．中国骨质疏松杂志，1998，4(4)：73-77
32．李继斌．骨量影响因素研究进展．国外医学卫生学分册，2000，27(4)：213-217
33．程浩，曲世平，董砚虎．骨质疏松的分子遗传学研究进展．国外医学遗传学分册，2002，25(1)：59-62
34. Ebesen EN et al.J Bone Miner Res, 1999,14:1394-1403
35. Johansson AG. et al.J Clin Endocrinol Metab, 1999,84:2002-2007
36．刘宗传，杨俊杰．环境因素对大、小鼠及其动物实验的影响．动物科学与动物医学，2000，17(5)：36-37
37．杨恒东．笼养蛋鸡骨质疏松症的病因及诊治．中国家禽，1998，1：27-28
38. Whitehead C C. Nutrition and skeletal discorsers in broilers and layers. Poultry International, 1995,10:40-48
39．申林才，姚四新译．鸡的营养与骨骼疾病．国外畜牧科技，1996，23：454-55
40. Feyan J H M, Elford P, Dipadova F E, et al.Interleukin- 6 is produced by bone and modulated by parathyroid hormone. J Bone Miner Res, 1989,4:633
41. Elias JA, Lentz V. IL-1 and tumor necrosis factor synergistically stimulate fibroblast IL-6 production and stabilize IL-6 messenger RNA. J Immunol, 1990,145:161
42. Ishimi Y, Miyacwa C, Jin C H, et al. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol, 1990,145:3297
43．陈百成，张洪斌，张汉杰，et al．生长因子对软骨细胞的作用．中华骨科杂志，1999：19(12)：746-747
44．原超，庄洪．β转化生长因子在骨质疏松症中的作用．中国中医骨伤科杂志，2001，9(6)：56-57
45．曲连芳，楮桂芳．家禽的骨骼疾病．辽宁畜牧与兽医，1995，1：31-33
46. Zhu Xing, Hou Jiafa, Shen Xiangzhen, et al. Influence of low calcium dietary on skeletal microstructure and bone mineral content in cage layer. Chin Poultry, 2001,23(16):11-13
47. Zhang Xiao-shuang, Tang-Jian, Qu-Julan. Study on cancellous bone distal femur in ovariectomized rats by Scanning Electron Microscope (SEM).Journal of Zhanjiang Normal College(natural sciences),2000,21(1):33-36
48．邓益锋．维生素D_3对青年蛋鸡骨代谢的影响及中药对笼养蛋鸡骨质疏松症的防治．南京农业大学硕士论文，2001
49．朱晓英．低磷及依普拉芬对笼养蛋鸡骨代谢、内分泌及生产的影响．南京农业大学硕士论文，2000
50．朱金娈，邹晓庭．新型饲料抗氧化剂-天然黄酮类化合物的研究进展．饲料研究，2001，9：8-12
51. Xu Deping, Jiang Hanhu, Xiao Kai, et al.Isolation, identification of isoflavones in soybean and their antioxidant abilities. Journal of Nanjing Agricultural University, 2001,24(3):89-92
52．毛红霞，许梓荣，占秀安．黄酮类化合物在动物营养中的研究及应用．饲料研究，2000，11：15-16
53. Chen Jie, Yang Guoyu, Han Zhengkang. Effect of daidzein on serum testosterone and rumen digestion, metabolism in ruminates. Jiangsu Agricultural Research, 1999, 20(2):17-19
54. Wang Genlin, Chen Jie. Effect of daidzein on LH secretion in ovariectomized gilts. Chin J Appl Physiol, 1998,14(1):70-73
55. Wang Genlin, Chen Jie, Chen Weihua, et al. Effect of daidzein on secretion of GnRH, LH and inhibin in gilts. Jiangsu J of Agr Sci, 1999,15(1):26-29
56. Liu Gentao, Chen Jie, Han Zhengkang. Effects of isoflavonic phytoestrogen daidzein to lactating sows. Animal Husbandry and Veterinary Medicine, 1997,29(1):5-7
57. Gao Feng, Zhou Guanghong, Han Zhengkang. Effect of diet supplemented with daidzein on growth performances and immune function in male chicks. China Poultry, 2000, 22(10):8-9
58．刘建中，林映才，郑黎．异黄酮类化合物在动物中的作用研究．兽药与饲料添加剂，1999，4：4-5
59．郑高利．大豆异黄酮的药理作用Ⅱ．中国现代应用药学杂志，1998，15(2)：9-11
60．郑高利．大豆异黄酮的药理作用Ⅰ．中国现代应用药学，1998，15(1)：4-5
61．邱永军，段焰，向天成．大豆异黄酮的功能特性．粮油食品科技，2002，10(1)：40-41
62. Guo Huijun, Han Zhengkang, Wang Guojie. Effect of daidzein supplemented in diet on the growth performance and related endocrine function in male rats. Journal of Nanjing Agricultural University, 2001,24(4):59-61
63．华辉，郭勇．黄酮类化合物药理研究进展．广东药学，1999，9(4)：9-12
64. Tang Rong, Fan Ruixia. Advances in research of the anticancer effects of soybean isoflavones. Chin Pharm J, 1999,34 (7): 435-438
65．韩正康．异黄酮类植物雌激素-大豆黄酮对雄性动物生长及有关内分泌的研究．畜牧与兽医，2000，2(1)：1-3
66．楼洪兴，黄昌成，周小平等．大豆素在猪日粮中的应用．中国饲料，2000，14：10-11
67．陈晓光，胡薇．大豆异黄酮与大豆“生命素”．大豆通报，1999，4：27
68. Adams N R. Permanent infertility in ewes exposed to plant estrogens. Aus Vet J, 1990,67:197-201
69. Liu Gentao, Zheng Yuanlin, Chen Weihua, et al. Effect of daidzein fed to pregnant sows on milk production and the levels of hormones in colostrums. Journal of Nanjing Agricultural University, 1998,22:69-72
70. Zhou Yu-chuan, Zhao Ru-qian, Lu-Lizhi, et al. Effect of daidzein on egg laying performance and hormone levels in serum of Shaoxing ducks during the late stage of egg production cycle. J of N.A.U.,2002,25(1):73-76
71．郑元林，艾晓杰，刘根桃等．大豆黄酮对大鼠肝脏氮代谢和胰岛素样生长因子生成和分泌的影响．华中农业大学学报，2002，21(1)：50-54
72. Wang Genlin, Chen Jie, N. Parvizi. Effect of Daidzein on LH secretion in the superfusion system of anterior pituitary tissue from goettingen miniature gilts. J of N.A.U.,1997,20(4):48-53
73．张荣庆，韩正康．黄酮类化合物对小鼠免疫功能和血中β-内啡肽水平的影响．中国免疫学杂志，1994，10(2)：91-92
74．刘根桃，郑元林，陈伟华等．妊娠后期母猪饲喂大豆黄酮对泌乳性能及初乳中激素水平的影响．南京农业大学学报，1998，22：69-72
75. Ke Ye-yan, Wang Guo-jie, Han Zheng-kang. Effects of daidzein on the Performance and Serum Hormone Concentrations in the Laying Quails. Acta Veterinaria of Zootechnica Sinica, 2002,33(3):243-246
76. Han Zhengkang, Wang Guojie. Isoflavone phytoestrogens: pespective on the development and application of nutritional bio-sciences in ruminants. Acta Zoonutrimenta Sinica, 1999, Supple(Ⅱ):65-68
77. Wang Yue-ying, Wang Yan-ling, Dong Xiu-tian, et al. Effects of cysteamine on mammary development in dairy goats. Acta Zoonutrimenta
Sinica, 1999,11, Supple:144-148
78. He Fujin, Wang Jian, Wang Jifeng, et al.Effects of genistein and daidzein on the proli- feration of human breast cancer cell line in vitro. Journal of Beijing University of TCM, 2002,25(1):22-25
79．李文亮，宋丹凤，崔洪斌．大豆异黄酮植物雌激素样生物活性研究进展．大豆通报，2002，3：19-20
80．张殿明，余隆绍．神经内分泌学．北京：中国医药科技出版社，1991，247-261
81. Ziegler J. Soybeans show promise in cancer prevention. News, 1994,86(22):1666-1667
82. Saloniemi H, Wahala K, Nykanen-Kurki P, et al. Phytoestrogen content and estrogenic effect of legume fodder. Proc Soc Exp Biol Med, 1995,208(1):13-17
83. Kaldas R S, Hughes C L Jr. Reproductive and general metabolic effects of phytoestrogens in mammals. Reprod Toxicol, 1989,3:81-89
84. Constantinou A, Kiguchik, Huberman E. Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res, 1990,50:2618
85. Aronson WJ, Tymebuk CN, Elashoff RM, et al. Decreased growth of human prostate LNCaP tumors in SCID mice fed a low fat, soy protein diet with isoflavones. Nutr Cancer, 1999,35(2):130-136
86．上海市医学化验所主编．临床生化检验．上海科技出版社，1998，224，354
87. Yan C H, Han R. Suppression of adhesion-induced protein tyrosine phosphorylation decreases invasive and metastatic potentials of B16-BL6 melanoma cells by protein tyrosine kinase inhibitor genistein. Invasion Metastasis, 1997,17:189
88. He Fujin, Wang Jian, Wang Jifeng, et al. Effects of genistein and daidzein on the prolix-feration of human breast cancer cell line in vitro. Journal of Beijing University of TCM, 2002,25(1):22-25
89. Peterson G. Evaluation of the biochemical targets of genistein in tumor cells. J Nutr, 1995,125: 784s
90. Yan Chunhong, Han Rui. Protein tyrosine kinase inhibitor Gn suppresses in vitro invasion of HT1080 human fibrosarcoma cells. Chin J Oncol,1999,21(3):171-174
91. Zhang Qinghong, Hu Yuzhen, Zhou Shisheng, et al. Inhibitory effect of genistein on the proliferation of the anterior pituitary cells of rats. Acta Physiologica Sinica. 2001,53(1):51-54
92．杨镇洲，糜漫天，朱俊东，等．转化生长因子β在大豆异黄酮抑制乳腺癌细胞增殖中的作用．营养学报，2001，23(1)：66-69
93. Wang G L, Chen Jie, Parvizi N. LH secretion following single injection and plantation of daidzein in ovariectomized gilts. 2nd Asian Symposium on Animal Biotechnology, Proceedings, 1995,422-437
94. Yang Zheng-rong, Cheng Tian-min, Su Yong-ping, et al. Study on anti-proliferation effects of genistein on MCF-7 and its selective effects on different cells. Acta Academiae Medicinae Militaris Tertiae, 2002,24(1):62-65
95．张响英，王根林．植物雌激素的免疫调节作用．畜牧与兽医，2000，32(3)：40-42
96. Arimandi BH, Alekel L, Hollis BW, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutri, 1996,126 (1):161-164
97．闫祥华，顾景范，孙存普，等．大豆异黄酮对大鼠血脂和过氧化状态的影响．营养学报，2000，22(1)：31-34
98．史琳娜，苏宜香．大豆异黄酮类对去卵巢大鼠骨丢失的影响．营养学报，2000，22(2)：113-117
99. Brandi M L. Natural and synthetic isoflavone in the prevention and treatment of chronis diseases. Italy, 1996 World Congress on Osteoporosis
100. Harvos, Ryozo Y. Study on Zoospore-attractivity Attivity Synthesis of Isoflavone and Their Actracting to Aphanomy as Eutiches Zoospore [J].Chem Pharm Bull,1998, 36(12):4876-4880
101. Fanti P, Monier- Faugere MC, Geng Z, et al. The Phytoestrogen genistein reduces bone loss in short-term ovariectomized rats[J].Osteoporos Int, 1998,8(3):274
102. Blair HC, Jordan SE, Peterson TG, et al. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats[J].J Cell Biochem, 1996,61(4):629
103. Liu Yin-yan, Fan Zhong-Xin, Yu Hong-bo. Synthesis of ipriflavone. Chin Pharm J, 2000,35(6):418-419
104. Gennari C. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Italy, 1996 World Congress on Osteoporosis
105. Reginster J Y. Role of ipriflavone in prevention and treatment of osteoporosis. USA, 1996 World Congress on Osteoporosis
106．韩祖斌，林华，邓思清，等．异黄酮类植物雌激素依普拉分对骨代谢的作用．中国骨质疏松杂志，1999，5(3)：47-50
107. Gambacciani M.Jpriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH - Agonist. Italy, 1996 World Congress on Osteoporosis
108. Agmisdeo D. Effect of ipriflavone in established osteoporosis and long-term safety. Italy, 1996 World Congress on Osteoporosis
109. Civitell R. In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. USA, 1996 World Congress on Osteoporosis
110. Mazzuoli GF. Inhibitory effect of ipriflavone on vertebral bone mass loss in postmenopausal women with low bone mass. Italy, 1996 World Congress on Osteoporosis
111. Iwao Yamazaki, Masako Kinoshita. Calcitonin secreting property of ipriflavone in the presense of estrogen. Life Science, 1986,38:1535-1541
112. Iwao Yamazaki. Effect of ipriflavone on the response of uterus and thyroid to estrogen. Life Science, 1986,38:757-764
113. Wasserman RH, Jaylor AN. Vitamin D_3-Induced Calcium-Binding Protein Chick Intestinal Mucosa. Science, 1966,152(6):791-793
114. Levai F, Szatmari I. Metabolism of ipriflavone. Acta pharm Hung, 1995,65(6):215
115. Levai F, Szatmari I. Pharmacokinetics of ipriflavone. Acta pharm Hung, 1995,65(6): 219
116. Cheng SL, Zhang SF, Nelson TL, et al. Stimulation of human osteoblast differentiation and function by Ipriflavone and its metabolites[J].Calcif Tissue Int, 1994, 55(5):356
117. Li Shu-qin, Pan Li-li, Liu Ying-min, et al. Biochemistry monitoring in patients with postmenopausal osteoporosis after ipriflavone intake. Chin Pharm J, 2000, 35(12):849-851
118. Maria luisa Brandi. Ipriflavone in vitro and in vivo effects on bone metabolism. Osteoporsis, Academic Press Inc, 1996, 1335-1342
119. Shi Mingjian, Liu Weiwan, Li Zongtao, et al. Effect of ipriflavone on ovariectomy-induced osteoporosis in rats. Chinese Journal of Osteoporosis, 1996,2(1):70-72
120．韦永中，陶松年，包丽华等．依普拉芬对去势大鼠骨丢失防治作用的试验研究．南京医科大学学报，1999，19(2)：134-135
121. Geris K L, Berghman L R, Kuhn E R, et al.Pre-and posthatch development changes in hypothalamic thyrotropin-releasing hormone and somatostatin concentration and in circulating growth hormone and thyrotropin levels in the chicken. J Endocrinology, 1998,159:219-225
122. Koves K, et al.Gonadotropin-releasing hormone binding sites in ovaries of normal cycling and persistent-estrus rats. Biol Reprod, 1989,41:505-511
123. Thatcher W W, et al.New clinical uses of GnRH and its analogues in cattle. Anim Reprod Sci, 1993,33:27-49
124. Johnson P A, Dickerman R W, Bahr J M. Decreased glanuloca cell luteinizing hormone sensitivity and altered thecal estradiol concentration in the aged hen. Gallus domesticus. Biology of Reproduction, 1986,35:641-646
125. Asem, E K. Influence of follicular maturation on ovarian steroidogenesis. Poultry Abstracts, 1987,13:41-48
126. Asem, E K, Hertelendy F. Role of calcium in luteinizing hormone-induced progesterone and cyclic AMP production in granuloca cells of the hen (Gallus domesticus). General and Comparative Endocrinology, 1986,62:120-128
127. Calvo F O, et al. LH stimulable adenylyl cyclase activity during the ovarlatory cycle in granuloea cells of the three largest follicle of the domestic hen. Bio Reprod, 1981,25:805-812
128．李鉴轩主编．家畜生理学．青海人民出版社，1992
129. William H, Burke. "Avian reproduction" in "DUCK' S PHYSIOLOGY OF DOMESTIC ANIMALS" (tenth edition) edited by Melvin. J. Swensow, 1984,847-862
130. Wang Genling, Zhao Zhihui, Chen Weihua, et al. Effects of daidzein on GnRH receptor level in pituitaries of piglets. Jiangsu J of Agr Sci, 2000,16(4):233-236
131. Wang Genlin, Chen Jie. Effect of daidzein on LH secretion in ovariectomized gilts. Chin J Appl Physiol, 1998,14(1):70-73
132. Harvey S, Lam S, Hall T R. Somatostatin tonically inhibits growth hormone secretion in domestic fowl. J of endocrinology, 1986,111:91-97
133. Peng C, et al. Expression and regulation of gonadotrpin-releasing hormone(GnRH) and GnRH receptor messenger ribonucleic acid in human granulose-luteal cells. Endocr, 1994,35:1740-1746
134. Heber D, et al. Ovary receptor binding activity of gonadotropin releasing hormone in rat. Am J Physiol, 1978,4:227
135. Wang Yanling, Han Zhengkang. Effects of cysteamine on mammary gland development and blood levels of somatostatin and growth hormone in pregnant rats. Journal of Nanjing Agricultural University, 1998,21(1): 87-90
136. Liu Xijie, Han Zhengkang, Ai Xiaojie. Oral route cysteamine induced changes of growth hormone insulin likegrowth factor-Ⅰ and somatostatin concentration in the peripheral blood of sheep. Hei Longjiang Animal Husbandry and Veterinary Medicine, 1997,12:1-3
137. Wang Yanling, Han Zhengkang. Effects of cysteamine on milk yield and several hormones levels of blood in rats at late stage of lactation. Zoological Research, 1998,19(3):247-249
138. Han Zhengkang, Liu Zongzhu, Shen Yanfa. Cysteamine induced changes of β-END and metabolic hormones concentration in the peripheral blood of sheep. Acta Veterinaria et Zootechnica Sinica, 1996,27(3):193-198
139. Cui Li, Lu Tianshui, Chen Feng, et al. Effects of cysteamine-preparation on dairy performance. J of Shanghai Jiaotong University(Agricultural Science),2001, 19(4): 274-275
140. Liu Zongzhu, Wang Jinbao, Xu Dewu, et al. Stablity of cysteamine and its effects on ruminal fermentation in vitro. Acta Veterinaria et Zootechnica Sinica, 1998,29 (6) :513-516
141. Wang Yanling, Han Zhengkang. Effects of cysteamine on rat milk yield and several hormones levels in blood and tissues. Chin J Appli Physiol, 1998,14(1):46-49.
142. Millad W J. Cysteamine-induced depletion of somatostatin and prolattin. Federation Proc, 1988,44:2546-2257
143. Szabo S, Rechlin S. Somatostatin in rat tissue is depleted by cysteamine administration. Endocrinology, 1981,109:2255-2257
144．刘建文，施用晖，乐国伟．半胱胺在动物研究中的应用．饲料博览，2001，6：7-9
145. Trenkle A .Hormonal and nutritional interrelationships and their effects on skcletal muscle . J Anim Sci, 1974,38:1142
146．陈仲达，刘宗柱．生长抑素研究及生长抑素抑制剂—半胱胺促畜禽生长应用综述．饲料与添加剂，2001，2：48-49
147．陈仲达，刘宗柱．生长抑素研究及生长抑素抑制剂—半胱胺促畜禽生长应用．饲料博览，2001，2：11-12
148. Wronski T J, Dann L M, Horner S L. Time course of vertebral osteopenia in ovariectomized rats. Bone, 1989,10:295
149. Kalu D N. The ovariectomized rat model of postmenopausal bone loss. Bone Miner, 1991,15:175
150. Hu Zhenming, Dai Kerong, Zhu Hanmin. Ovariectomy effect on bone mineral density in rats. Academic Journal of Kunming Medical College, 1997,18(4):14-17
151．陈槐卿，李良，郑虎．绝经后骨质疏松的动物模型．中国骨质疏松杂志，1999，4(2)：82-85
152. Liang Xiaoping, Dong Shaohong, Xiao Xuelu, et al. An experimental study of IGF-Ⅰ and TGF-β_1 in osteoporosis rat. 中国老年学杂志,2002,22:47-49
153．谭达全，曾英，莫新民．去卵巢后雌性大鼠骨质疏松症模型骨量及骨强度的变化．中国中医基础医学杂志，2000，6(2)：24-27
154．陈金标，秦林林，张卫等．体重、体成分与骨密度的关系．中国骨质疏松杂志，1997，3
(2)：15-18
155．程国钧，袁艺，刘建立等．北京市地区1400例腰椎骨量与年龄和绝经关系．中华妇产科杂志，1997，32(9)：532-534
156. Wronski T J, Schenck P A, Walsh C C. Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue Int, 1987,40:155-159
157. Dorothy T et al.Am J Clin Nutr, 1998,68:749-754
158. Manzoni P et al. Am J Clin Nutr, 1996,64:603-607
159. Wang Guojie, Han Zhengkang, Chen Weihua. Effects of daidzein on muscle growth and some endogenous hormone levels in rats. Zoological Research, 1995,16(1):23-29
160. Ma Jingfu, Wang Wenzhi, Yang Dingzhou, et al. Relationship between weight, Height, body mass index and BMD in postmenopausal women. Chinese Journal of Osteoporosis, 1998,4(4):27-29
161. May H, Murphy S, Khaw K T. Age-associated bone loss in men and women and its relationship to weight. Ageing, 1994,23:235
162. Li Xiaodong, Tetsuo Inoue. Evaluation bone mass of rats by dual energy X-ray absor-ptiometry:influence of body weight and naso-anal length. Chinese Journal of Osteoporosis. 1995,1(1):21-24
163. Yan Zhongfu, Zhong Ming, Zhu Guangrong, et al.A new method for measuring bone mineral density of rat models. Chinese Journal of Osteoporosis, 1996,2(3):4-6
164．翁世芳，黄克，王洪复．大鼠骨密度测定在骨质疏松模型研制中的应用．西安全国第二届骨质疏松专业会，1994：270-272
165．张皎，侯加法．兽医临床上几种无损伤骨矿测定方法简介．畜牧与兽医，2002，34(3)：38-40
166．王艳林，韩正康．大豆黄素对生长猪的生产性能和血液免疫指标的影响．饲料博览，2001，6：4-6
167．周振雷．笼养蛋鸡骨质疏松症防治的研究．南京农业大学硕士论文，2003
2．奚德华．猪骨软骨病关节软骨显微、超微结构变化及其相关细胞因子表达的研究．南京农业大学硕士论文，2003，9-11
3．金世鑫，汪耀，沈志卫．骨质疏松综合征：骨组织学和临床的联系(三)．中国骨质疏松杂志，1997，3(2)：62-65
4．于世凤．破骨细胞与骨吸收．中国骨质疏松杂志，1997，3(2)：72-74
5. Cheven B A A, Visser J W W, Nijuweide P J. In vitro osteoclast generation from different bone marrow fractions, including a highly enriched hemopoietic stem cell population. Nature, 1986,321:79-81
6．姜宏卫，程浩，董砚虎．骨形成调控机制研究进展．Foreigh Medical Sciences·Section of Pathophysiology and clinical Medicine. 2002,22(3):222-225
7. Zeng Ying, Mo Xinmin, Hong Jing. Experimental study on the role of calcium
phosphorus and calcium regulation hormone in the postmenopausal osteoporosis rats. 中国中医骨伤科杂志, 2001, 9 (5): 25-27
8. Horowitz Mc. Cytokines and estrogen in bone: anti-osteoporotic effects. Science, 1993, 260: 626.
9. McDonnell. D P, Norris J D. Analysis of the molecular pharmacology of estrogen receptor agonists and antagonists provides insights into the mechanism of action of estrogen in bone. Osteoporosis, 1997, Suppl 1:S29
10. Claude D. Arnaud, Sarah D. Sanchez. Calcium and Phosphorus. Present Knowledge in Nutrition. 1998,4:238-247
11. Wu Bo, Xu Bin, Huang Tianyou, et al. Changes of bone metabolism and the effects of estrogen treatment in ovariectomized rats. Chinese Pharmacological Bulletin, 1997,13(2):163-166
12. Liu Guangyao, Liu Fengyang. Use of calcitonin to treat osteoporosis in OVX rats. Chinese Journal of Osteoporosis, 1997, (3):15-17
13. An Shengjun, Li Tao, Li En. Effect of kidney-tonifying herbs on ovary function and bone mass in postmenopausal women. Chinese Journal of Osteoporosis, 2000, 6(2):55-59
14. Li Liang, Chen Huaiqing, He Changming, et al. Bone histomorphometry and bone mineral density changes in ovariectomized goats at regular intervals. Chinese Journal of Osteoporosis, 2000,6(2):10-12
15．乔伟伟，许兰文．骨质疏松症大鼠模型．上海试验动物科学，1997，17(3)：174-176
16. Anthony W, Norman. Vitamine D Present Knowledge in Nutrition. 1998,4:116-122
17．薛延．骨质疏松症诊断与治疗指南．北京：科学出版社，1999，432-454
18. Couch JR .Cage Layer Fatigue. Feed Age ,1995(5): 55-57
19. Ornoy A, Goodwin D, Noff D, and Edelstein S. 24,25-dihydroxyvitamin D is a metabolite of Vitamin Dessential for bone formation. Nature, 1978,276:517-519
20. Schwarta Z, Schlader DL, Swain LD, et al. Direct effect of 1,25-dihydroxyvitamin D_3 on growth zone chondrocyte membrane alkaline phosphatase and phospholipase-A_2 Specific activities. Endocrinology, 1988, 123:2878-2884
21. Markes SC Jr, Popoff SN. Bone cellbiology: The regulation of development, structure and function in skeleton. American Journal of Anatomy, 1988,183:1-44
22. Whitehead CC. Bone Biology and Skeletal Discorders in Poultry. Carfax Company, Oxfordor-shire , England, 1992, 182-280
23．韩正康，毛鑫智等编．家禽生理学．江苏科技出版社．1986，117
24．刘忠厚．骨质疏松学．北京：科学出版社，1998，109
25. Shugbrue P J, Dorsa D M. Estrogen modulates the growth-associated protein GAP-43 (neuromodulin) mRNA in the rat preoptic area and basal hypothalamus. Neuroendocrinology, 1993, 57(3):439-447
26. Mayer M, Rosin F. Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol. Am J Physiol, 1975,229:138
27．姜振玲．雌性激素影响大鼠生长激素结合蛋白水平．生理科学进展，1994，25(3)：222
28. Lindsay R, Hart D M, Aitken J M, et al. Lone term prevention of postmenopausal osteoporosis by estrogen. Lancert, 1976,1:1038
29．姜晓洪．雌激素抗骨质疏松的研究现状．医师进修杂志，2002，25(4)：55-56
30．孙兰，汪青，刘景生．雌激素促进人的类成骨细胞TE-85成骨作用的受体机制．药学学报，1999，34(8)：561-564
31．赵燕灵，朱传英，丁桂芝等．原发性骨质疏松症的发病机理．中国骨质疏松杂志，1998，4(4)：73-77
32．李继斌．骨量影响因素研究进展．国外医学卫生学分册，2000，27(4)：213-217
33．程浩，曲世平，董砚虎．骨质疏松的分子遗传学研究进展．国外医学遗传学分册，2002，25(1)：59-62
34. Ebesen EN et al.J Bone Miner Res, 1999,14:1394-1403
35. Johansson AG. et al.J Clin Endocrinol Metab, 1999,84:2002-2007
36．刘宗传，杨俊杰．环境因素对大、小鼠及其动物实验的影响．动物科学与动物医学，2000，17(5)：36-37
37．杨恒东．笼养蛋鸡骨质疏松症的病因及诊治．中国家禽，1998，1：27-28
38. Whitehead C C. Nutrition and skeletal discorsers in broilers and layers. Poultry International, 1995,10:40-48
39．申林才，姚四新译．鸡的营养与骨骼疾病．国外畜牧科技，1996，23：454-55
40. Feyan J H M, Elford P, Dipadova F E, et al.Interleukin- 6 is produced by bone and modulated by parathyroid hormone. J Bone Miner Res, 1989,4:633
41. Elias JA, Lentz V. IL-1 and tumor necrosis factor synergistically stimulate fibroblast IL-6 production and stabilize IL-6 messenger RNA. J Immunol, 1990,145:161
42. Ishimi Y, Miyacwa C, Jin C H, et al. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol, 1990,145:3297
43．陈百成，张洪斌，张汉杰，et al．生长因子对软骨细胞的作用．中华骨科杂志，1999：19(12)：746-747
44．原超，庄洪．β转化生长因子在骨质疏松症中的作用．中国中医骨伤科杂志，2001，9(6)：56-57
45．曲连芳，楮桂芳．家禽的骨骼疾病．辽宁畜牧与兽医，1995，1：31-33
46. Zhu Xing, Hou Jiafa, Shen Xiangzhen, et al. Influence of low calcium dietary on skeletal microstructure and bone mineral content in cage layer. Chin Poultry, 2001,23(16):11-13
47. Zhang Xiao-shuang, Tang-Jian, Qu-Julan. Study on cancellous bone distal femur in ovariectomized rats by Scanning Electron Microscope (SEM).Journal of Zhanjiang Normal College(natural sciences),2000,21(1):33-36
48．邓益锋．维生素D_3对青年蛋鸡骨代谢的影响及中药对笼养蛋鸡骨质疏松症的防治．南京农业大学硕士论文，2001
49．朱晓英．低磷及依普拉芬对笼养蛋鸡骨代谢、内分泌及生产的影响．南京农业大学硕士论文，2000
50．朱金娈，邹晓庭．新型饲料抗氧化剂-天然黄酮类化合物的研究进展．饲料研究，2001，9：8-12
51. Xu Deping, Jiang Hanhu, Xiao Kai, et al.Isolation, identification of isoflavones in soybean and their antioxidant abilities. Journal of Nanjing Agricultural University, 2001,24(3):89-92
52．毛红霞，许梓荣，占秀安．黄酮类化合物在动物营养中的研究及应用．饲料研究，2000，11：15-16
53. Chen Jie, Yang Guoyu, Han Zhengkang. Effect of daidzein on serum testosterone and rumen digestion, metabolism in ruminates. Jiangsu Agricultural Research, 1999, 20(2):17-19
54. Wang Genlin, Chen Jie. Effect of daidzein on LH secretion in ovariectomized gilts. Chin J Appl Physiol, 1998,14(1):70-73
55. Wang Genlin, Chen Jie, Chen Weihua, et al. Effect of daidzein on secretion of GnRH, LH and inhibin in gilts. Jiangsu J of Agr Sci, 1999,15(1):26-29
56. Liu Gentao, Chen Jie, Han Zhengkang. Effects of isoflavonic phytoestrogen daidzein to lactating sows. Animal Husbandry and Veterinary Medicine, 1997,29(1):5-7
57. Gao Feng, Zhou Guanghong, Han Zhengkang. Effect of diet supplemented with daidzein on growth performances and immune function in male chicks. China Poultry, 2000, 22(10):8-9
58．刘建中，林映才，郑黎．异黄酮类化合物在动物中的作用研究．兽药与饲料添加剂，1999，4：4-5
59．郑高利．大豆异黄酮的药理作用Ⅱ．中国现代应用药学杂志，1998，15(2)：9-11
60．郑高利．大豆异黄酮的药理作用Ⅰ．中国现代应用药学，1998，15(1)：4-5
61．邱永军，段焰，向天成．大豆异黄酮的功能特性．粮油食品科技，2002，10(1)：40-41
62. Guo Huijun, Han Zhengkang, Wang Guojie. Effect of daidzein supplemented in diet on the growth performance and related endocrine function in male rats. Journal of Nanjing Agricultural University, 2001,24(4):59-61
63．华辉，郭勇．黄酮类化合物药理研究进展．广东药学，1999，9(4)：9-12
64. Tang Rong, Fan Ruixia. Advances in research of the anticancer effects of soybean isoflavones. Chin Pharm J, 1999,34 (7): 435-438
65．韩正康．异黄酮类植物雌激素-大豆黄酮对雄性动物生长及有关内分泌的研究．畜牧与兽医，2000，2(1)：1-3
66．楼洪兴，黄昌成，周小平等．大豆素在猪日粮中的应用．中国饲料，2000，14：10-11
67．陈晓光，胡薇．大豆异黄酮与大豆“生命素”．大豆通报，1999，4：27
68. Adams N R. Permanent infertility in ewes exposed to plant estrogens. Aus Vet J, 1990,67:197-201
69. Liu Gentao, Zheng Yuanlin, Chen Weihua, et al. Effect of daidzein fed to pregnant sows on milk production and the levels of hormones in colostrums. Journal of Nanjing Agricultural University, 1998,22:69-72
70. Zhou Yu-chuan, Zhao Ru-qian, Lu-Lizhi, et al. Effect of daidzein on egg laying performance and hormone levels in serum of Shaoxing ducks during the late stage of egg production cycle. J of N.A.U.,2002,25(1):73-76
71．郑元林，艾晓杰，刘根桃等．大豆黄酮对大鼠肝脏氮代谢和胰岛素样生长因子生成和分泌的影响．华中农业大学学报，2002，21(1)：50-54
72. Wang Genlin, Chen Jie, N. Parvizi. Effect of Daidzein on LH secretion in the superfusion system of anterior pituitary tissue from goettingen miniature gilts. J of N.A.U.,1997,20(4):48-53
73．张荣庆，韩正康．黄酮类化合物对小鼠免疫功能和血中β-内啡肽水平的影响．中国免疫学杂志，1994，10(2)：91-92
74．刘根桃，郑元林，陈伟华等．妊娠后期母猪饲喂大豆黄酮对泌乳性能及初乳中激素水平的影响．南京农业大学学报，1998，22：69-72
75. Ke Ye-yan, Wang Guo-jie, Han Zheng-kang. Effects of daidzein on the Performance and Serum Hormone Concentrations in the Laying Quails. Acta Veterinaria of Zootechnica Sinica, 2002,33(3):243-246
76. Han Zhengkang, Wang Guojie. Isoflavone phytoestrogens: pespective on the development and application of nutritional bio-sciences in ruminants. Acta Zoonutrimenta Sinica, 1999, Supple(Ⅱ):65-68
77. Wang Yue-ying, Wang Yan-ling, Dong Xiu-tian, et al. Effects of cysteamine on mammary development in dairy goats. Acta Zoonutrimenta
Sinica, 1999,11, Supple:144-148
78. He Fujin, Wang Jian, Wang Jifeng, et al.Effects of genistein and daidzein on the proli- feration of human breast cancer cell line in vitro. Journal of Beijing University of TCM, 2002,25(1):22-25
79．李文亮，宋丹凤，崔洪斌．大豆异黄酮植物雌激素样生物活性研究进展．大豆通报，2002，3：19-20
80．张殿明，余隆绍．神经内分泌学．北京：中国医药科技出版社，1991，247-261
81. Ziegler J. Soybeans show promise in cancer prevention. News, 1994,86(22):1666-1667
82. Saloniemi H, Wahala K, Nykanen-Kurki P, et al. Phytoestrogen content and estrogenic effect of legume fodder. Proc Soc Exp Biol Med, 1995,208(1):13-17
83. Kaldas R S, Hughes C L Jr. Reproductive and general metabolic effects of phytoestrogens in mammals. Reprod Toxicol, 1989,3:81-89
84. Constantinou A, Kiguchik, Huberman E. Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res, 1990,50:2618
85. Aronson WJ, Tymebuk CN, Elashoff RM, et al. Decreased growth of human prostate LNCaP tumors in SCID mice fed a low fat, soy protein diet with isoflavones. Nutr Cancer, 1999,35(2):130-136
86．上海市医学化验所主编．临床生化检验．上海科技出版社，1998，224，354
87. Yan C H, Han R. Suppression of adhesion-induced protein tyrosine phosphorylation decreases invasive and metastatic potentials of B16-BL6 melanoma cells by protein tyrosine kinase inhibitor genistein. Invasion Metastasis, 1997,17:189
88. He Fujin, Wang Jian, Wang Jifeng, et al. Effects of genistein and daidzein on the prolix-feration of human breast cancer cell line in vitro. Journal of Beijing University of TCM, 2002,25(1):22-25
89. Peterson G. Evaluation of the biochemical targets of genistein in tumor cells. J Nutr, 1995,125: 784s
90. Yan Chunhong, Han Rui. Protein tyrosine kinase inhibitor Gn suppresses in vitro invasion of HT1080 human fibrosarcoma cells. Chin J Oncol,1999,21(3):171-174
91. Zhang Qinghong, Hu Yuzhen, Zhou Shisheng, et al. Inhibitory effect of genistein on the proliferation of the anterior pituitary cells of rats. Acta Physiologica Sinica. 2001,53(1):51-54
92．杨镇洲，糜漫天，朱俊东，等．转化生长因子β在大豆异黄酮抑制乳腺癌细胞增殖中的作用．营养学报，2001，23(1)：66-69
93. Wang G L, Chen Jie, Parvizi N. LH secretion following single injection and plantation of daidzein in ovariectomized gilts. 2nd Asian Symposium on Animal Biotechnology, Proceedings, 1995,422-437
94. Yang Zheng-rong, Cheng Tian-min, Su Yong-ping, et al. Study on anti-proliferation effects of genistein on MCF-7 and its selective effects on different cells. Acta Academiae Medicinae Militaris Tertiae, 2002,24(1):62-65
95．张响英，王根林．植物雌激素的免疫调节作用．畜牧与兽医，2000，32(3)：40-42
96. Arimandi BH, Alekel L, Hollis BW, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutri, 1996,126 (1):161-164
97．闫祥华，顾景范，孙存普，等．大豆异黄酮对大鼠血脂和过氧化状态的影响．营养学报，2000，22(1)：31-34
98．史琳娜，苏宜香．大豆异黄酮类对去卵巢大鼠骨丢失的影响．营养学报，2000，22(2)：113-117
99. Brandi M L. Natural and synthetic isoflavone in the prevention and treatment of chronis diseases. Italy, 1996 World Congress on Osteoporosis
100. Harvos, Ryozo Y. Study on Zoospore-attractivity Attivity Synthesis of Isoflavone and Their Actracting to Aphanomy as Eutiches Zoospore [J].Chem Pharm Bull,1998, 36(12):4876-4880
101. Fanti P, Monier- Faugere MC, Geng Z, et al. The Phytoestrogen genistein reduces bone loss in short-term ovariectomized rats[J].Osteoporos Int, 1998,8(3):274
102. Blair HC, Jordan SE, Peterson TG, et al. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats[J].J Cell Biochem, 1996,61(4):629
103. Liu Yin-yan, Fan Zhong-Xin, Yu Hong-bo. Synthesis of ipriflavone. Chin Pharm J, 2000,35(6):418-419
104. Gennari C. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Italy, 1996 World Congress on Osteoporosis
105. Reginster J Y. Role of ipriflavone in prevention and treatment of osteoporosis. USA, 1996 World Congress on Osteoporosis
106．韩祖斌，林华，邓思清，等．异黄酮类植物雌激素依普拉分对骨代谢的作用．中国骨质疏松杂志，1999，5(3)：47-50
107. Gambacciani M.Jpriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH - Agonist. Italy, 1996 World Congress on Osteoporosis
108. Agmisdeo D. Effect of ipriflavone in established osteoporosis and long-term safety. Italy, 1996 World Congress on Osteoporosis
109. Civitell R. In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. USA, 1996 World Congress on Osteoporosis
110. Mazzuoli GF. Inhibitory effect of ipriflavone on vertebral bone mass loss in postmenopausal women with low bone mass. Italy, 1996 World Congress on Osteoporosis
111. Iwao Yamazaki, Masako Kinoshita. Calcitonin secreting property of ipriflavone in the presense of estrogen. Life Science, 1986,38:1535-1541
112. Iwao Yamazaki. Effect of ipriflavone on the response of uterus and thyroid to estrogen. Life Science, 1986,38:757-764
113. Wasserman RH, Jaylor AN. Vitamin D_3-Induced Calcium-Binding Protein Chick Intestinal Mucosa. Science, 1966,152(6):791-793
114. Levai F, Szatmari I. Metabolism of ipriflavone. Acta pharm Hung, 1995,65(6):215
115. Levai F, Szatmari I. Pharmacokinetics of ipriflavone. Acta pharm Hung, 1995,65(6): 219
116. Cheng SL, Zhang SF, Nelson TL, et al. Stimulation of human osteoblast differentiation and function by Ipriflavone and its metabolites[J].Calcif Tissue Int, 1994, 55(5):356
117. Li Shu-qin, Pan Li-li, Liu Ying-min, et al. Biochemistry monitoring in patients with postmenopausal osteoporosis after ipriflavone intake. Chin Pharm J, 2000, 35(12):849-851
118. Maria luisa Brandi. Ipriflavone in vitro and in vivo effects on bone metabolism. Osteoporsis, Academic Press Inc, 1996, 1335-1342
119. Shi Mingjian, Liu Weiwan, Li Zongtao, et al. Effect of ipriflavone on ovariectomy-induced osteoporosis in rats. Chinese Journal of Osteoporosis, 1996,2(1):70-72
120．韦永中，陶松年，包丽华等．依普拉芬对去势大鼠骨丢失防治作用的试验研究．南京医科大学学报，1999，19(2)：134-135
121. Geris K L, Berghman L R, Kuhn E R, et al.Pre-and posthatch development changes in hypothalamic thyrotropin-releasing hormone and somatostatin concentration and in circulating growth hormone and thyrotropin levels in the chicken. J Endocrinology, 1998,159:219-225
122. Koves K, et al.Gonadotropin-releasing hormone binding sites in ovaries of normal cycling and persistent-estrus rats. Biol Reprod, 1989,41:505-511
123. Thatcher W W, et al.New clinical uses of GnRH and its analogues in cattle. Anim Reprod Sci, 1993,33:27-49
124. Johnson P A, Dickerman R W, Bahr J M. Decreased glanuloca cell luteinizing hormone sensitivity and altered thecal estradiol concentration in the aged hen. Gallus domesticus. Biology of Reproduction, 1986,35:641-646
125. Asem, E K. Influence of follicular maturation on ovarian steroidogenesis. Poultry Abstracts, 1987,13:41-48
126. Asem, E K, Hertelendy F. Role of calcium in luteinizing hormone-induced progesterone and cyclic AMP production in granuloca cells of the hen (Gallus domesticus). General and Comparative Endocrinology, 1986,62:120-128
127. Calvo F O, et al. LH stimulable adenylyl cyclase activity during the ovarlatory cycle in granuloea cells of the three largest follicle of the domestic hen. Bio Reprod, 1981,25:805-812
128．李鉴轩主编．家畜生理学．青海人民出版社，1992
129. William H, Burke. "Avian reproduction" in "DUCK' S PHYSIOLOGY OF DOMESTIC ANIMALS" (tenth edition) edited by Melvin. J. Swensow, 1984,847-862
130. Wang Genling, Zhao Zhihui, Chen Weihua, et al. Effects of daidzein on GnRH receptor level in pituitaries of piglets. Jiangsu J of Agr Sci, 2000,16(4):233-236
131. Wang Genlin, Chen Jie. Effect of daidzein on LH secretion in ovariectomized gilts. Chin J Appl Physiol, 1998,14(1):70-73
132. Harvey S, Lam S, Hall T R. Somatostatin tonically inhibits growth hormone secretion in domestic fowl. J of endocrinology, 1986,111:91-97
133. Peng C, et al. Expression and regulation of gonadotrpin-releasing hormone(GnRH) and GnRH receptor messenger ribonucleic acid in human granulose-luteal cells. Endocr, 1994,35:1740-1746
134. Heber D, et al. Ovary receptor binding activity of gonadotropin releasing hormone in rat. Am J Physiol, 1978,4:227
135. Wang Yanling, Han Zhengkang. Effects of cysteamine on mammary gland development and blood levels of somatostatin and growth hormone in pregnant rats. Journal of Nanjing Agricultural University, 1998,21(1): 87-90
136. Liu Xijie, Han Zhengkang, Ai Xiaojie. Oral route cysteamine induced changes of growth hormone insulin likegrowth factor-Ⅰ and somatostatin concentration in the peripheral blood of sheep. Hei Longjiang Animal Husbandry and Veterinary Medicine, 1997,12:1-3
137. Wang Yanling, Han Zhengkang. Effects of cysteamine on milk yield and several hormones levels of blood in rats at late stage of lactation. Zoological Research, 1998,19(3):247-249
138. Han Zhengkang, Liu Zongzhu, Shen Yanfa. Cysteamine induced changes of β-END and metabolic hormones concentration in the peripheral blood of sheep. Acta Veterinaria et Zootechnica Sinica, 1996,27(3):193-198
139. Cui Li, Lu Tianshui, Chen Feng, et al. Effects of cysteamine-preparation on dairy performance. J of Shanghai Jiaotong University(Agricultural Science),2001, 19(4): 274-275
140. Liu Zongzhu, Wang Jinbao, Xu Dewu, et al. Stablity of cysteamine and its effects on ruminal fermentation in vitro. Acta Veterinaria et Zootechnica Sinica, 1998,29 (6) :513-516
141. Wang Yanling, Han Zhengkang. Effects of cysteamine on rat milk yield and several hormones levels in blood and tissues. Chin J Appli Physiol, 1998,14(1):46-49.
142. Millad W J. Cysteamine-induced depletion of somatostatin and prolattin. Federation Proc, 1988,44:2546-2257
143. Szabo S, Rechlin S. Somatostatin in rat tissue is depleted by cysteamine administration. Endocrinology, 1981,109:2255-2257
144．刘建文，施用晖，乐国伟．半胱胺在动物研究中的应用．饲料博览，2001，6：7-9
145. Trenkle A .Hormonal and nutritional interrelationships and their effects on skcletal muscle . J Anim Sci, 1974,38:1142
146．陈仲达，刘宗柱．生长抑素研究及生长抑素抑制剂—半胱胺促畜禽生长应用综述．饲料与添加剂，2001，2：48-49
147．陈仲达，刘宗柱．生长抑素研究及生长抑素抑制剂—半胱胺促畜禽生长应用．饲料博览，2001，2：11-12
148. Wronski T J, Dann L M, Horner S L. Time course of vertebral osteopenia in ovariectomized rats. Bone, 1989,10:295
149. Kalu D N. The ovariectomized rat model of postmenopausal bone loss. Bone Miner, 1991,15:175
150. Hu Zhenming, Dai Kerong, Zhu Hanmin. Ovariectomy effect on bone mineral density in rats. Academic Journal of Kunming Medical College, 1997,18(4):14-17
151．陈槐卿，李良，郑虎．绝经后骨质疏松的动物模型．中国骨质疏松杂志，1999，4(2)：82-85
152. Liang Xiaoping, Dong Shaohong, Xiao Xuelu, et al. An experimental study of IGF-Ⅰ and TGF-β_1 in osteoporosis rat. 中国老年学杂志,2002,22:47-49
153．谭达全，曾英，莫新民．去卵巢后雌性大鼠骨质疏松症模型骨量及骨强度的变化．中国中医基础医学杂志，2000，6(2)：24-27
154．陈金标，秦林林，张卫等．体重、体成分与骨密度的关系．中国骨质疏松杂志，1997，3
(2)：15-18
155．程国钧，袁艺，刘建立等．北京市地区1400例腰椎骨量与年龄和绝经关系．中华妇产科杂志，1997，32(9)：532-534
156. Wronski T J, Schenck P A, Walsh C C. Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue Int, 1987,40:155-159
157. Dorothy T et al.Am J Clin Nutr, 1998,68:749-754
158. Manzoni P et al. Am J Clin Nutr, 1996,64:603-607
159. Wang Guojie, Han Zhengkang, Chen Weihua. Effects of daidzein on muscle growth and some endogenous hormone levels in rats. Zoological Research, 1995,16(1):23-29
160. Ma Jingfu, Wang Wenzhi, Yang Dingzhou, et al. Relationship between weight, Height, body mass index and BMD in postmenopausal women. Chinese Journal of Osteoporosis, 1998,4(4):27-29
161. May H, Murphy S, Khaw K T. Age-associated bone loss in men and women and its relationship to weight. Ageing, 1994,23:235
162. Li Xiaodong, Tetsuo Inoue. Evaluation bone mass of rats by dual energy X-ray absor-ptiometry:influence of body weight and naso-anal length. Chinese Journal of Osteoporosis. 1995,1(1):21-24
163. Yan Zhongfu, Zhong Ming, Zhu Guangrong, et al.A new method for measuring bone mineral density of rat models. Chinese Journal of Osteoporosis, 1996,2(3):4-6
164．翁世芳，黄克，王洪复．大鼠骨密度测定在骨质疏松模型研制中的应用．西安全国第二届骨质疏松专业会，1994：270-272
165．张皎，侯加法．兽医临床上几种无损伤骨矿测定方法简介．畜牧与兽医，2002，34(3)：38-40
166．王艳林，韩正康．大豆黄素对生长猪的生产性能和血液免疫指标的影响．饲料博览，2001，6：4-6
167．周振雷．笼养蛋鸡骨质疏松症防治的研究．南京农业大学硕士论文，2003