In search of an animal model for postmenopausal diseases.

In search of an animal model for postmenopausal diseases.
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寻找绝经后疾病的动物模型。

DOI:
--
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发表时间:
1998
期刊:
Frontiers in Bioscience
影响因子:
--
通讯作者:
A. Turner
A. Turner
中科院分区:
--
文献类型:
--
作者:
E. Thorndike;A. Turner

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本综述的目的是讨论使用老年切除卵巢的母羊作为一个具有成本效益的大型动物模型,研究冠状动脉疾病(CAD),骨质疏松症,骨关节炎(OA),和口腔骨丢失-绝经后看到的条件。我们实验室的早期研究表明,绵羊卵巢切除术后髂嵴的骨矿物质密度(BMD)显著下降,而随后的研究表明,卵巢切除术后腰椎的骨丢失(通过双能X线吸收测定法(DXA)测量)减少。我们研究了雌激素缺乏和雌激素治疗对老年卵巢切除(OVX)母羊的终末主动脉的影响,并证明与对照组相比,雌激素缺乏的动物的远侧主动脉内膜下增厚。研究OA的流行模型是内侧或外侧半月板切除后结合运动的绵羊膝关节,但需要雌激素缺乏的OA大型动物模型来研究绝经后发生的关节软骨变化。我们看到卵巢切除术对关节软骨的生物力学特性(聚合模量和剪切模量)的影响。雌激素缺乏对膝关节软骨有不利影响,即使OVX动物的软骨看起来大体正常。在另一项研究中,卵巢切除术后13.5个月,我们发现关节软骨的雌激素受体结合能力增加,表明关节软骨是性激素敏感组织。系统性骨质疏松症与下颌骨和上颌骨骨丢失之间的相关性引起了人们的强烈兴趣。我们使用DXA研究了OVX绵羊的下颌骨丢失。与假手术和雌二醇治疗的动物相比,OVX组的平均BMD较低,表明OVX母羊的全身骨丢失可能伴有口腔骨丢失。冠状动脉疾病,骨质疏松症,骨关节炎(OA)和口腔骨丢失都有重大影响妇女的健康绝经后,我们发现,这些条件的某些特征可以重现在卵巢成熟或老年雌激素缺乏羊。目前将绵羊作为研究雌激素缺乏症的唯一模型还为时过早,与小动物杂食动物和非人灵长类动物的许多差异需要克服,必须继续寻找更经济的模型。然而,这种模型可能提供了研究绝经后疾病以及新治疗药物的安全性和有效性的机会。
The purpose of this review is to discuss the use of the aged ovariectomized ewe as a cost-effective large animal model to study coronary artery disease (CAD), osteoporosis, osteoarthritis (OA), and oral bone loss--conditions seen after menopause. Earlier studies from our laboratory showed a significant decline in the bone mineral density (BMD) of the iliac crest following ovariectomy in sheep, while subsequent studies demonstrated decreased bone loss (measured by dual energy X-ray absorptiometry (DXA)) in the lumbar vertebrae following ovariectomy. We examined the effects of estrogen deficiency and estrogen therapy on the terminal aorta of the aged ovariectomized (OVX) ewes and demonstrated subintimal thickening in the distal aorta of animals that were estrogen deficient when compared to the control groups. A popular model to study OA is the knee joint of sheep following medial or lateral meniscus removal combined with exercise, but there is a need for an estrogen-deficient large animal model of OA to study articular cartilage changes occurring after menopause. We saw an effect of ovariectomy on the biomechanical properties (aggregate modulus and shear modulus) of articular cartilage. Estrogen deficiency had a detrimental effect on the articular cartilage of the knee even though the cartilage of the OVX animals appeared grossly normal. In another study, 13.5 months following ovariectomy, we found an increase in estrogen receptor binding capacity of the articular cartilage suggesting that articular cartilage is a sex-hormone sensitive tissue. There is intense interest in the correlation between systemic osteoporosis and bone loss of the mandible and maxilla. We studied mandibular bone loss in OVX sheep using DXA. The mean BMD of the OVX group versus sham and estradiol-treated animals was lower, indicating that systemic bone loss in OVX ewes may be accompanied by oral bone loss. Coronary artery disease, osteoporosis, osteoarthritis (OA) and oral bone loss all have a major impact on women's heath after menopause and we found that certain characteristics of these conditions can be reproduced in the skeletally mature or aged estrogen-deficient sheep. It is premature to promote the sheep as the only model to study estrogen deficiency and the many differences from small animal omnivores and non-human primates need to be overcome and a search for more economical models must continue. This model, however, may offer the opportunity to study postmenopausal conditions and the safety and efficacy of new therapeutic agents.
雌激素替代疗法的风险和益处:休闲世界。
DOI: --
发表时间: 1995
期刊: International journal of fertility and menopausal studies
影响因子: --
作者:
Paganini-Hill,A
通讯作者: Paganini-Hill,A
DOI: 10.1016/0021-9290(89)90069-9
发表时间: 1989-01-01
影响因子: 2.4
作者:
MOW, VC;GIBBS, MC;ATHANASIOU, KA
通讯作者: ATHANASIOU, KA