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
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