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使用小型猪建立骨质疏松动物模型

Development of osteoporosis animal model using micropigs.

作者信息

Kim Sang-Woo, Kim Kyoung-Shim, Solis Chester D, Lee Myeong-Seop, Hyun Byung-Hwa

机构信息

Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.

出版信息

Lab Anim Res. 2013 Sep;29(3):174-7. doi: 10.5625/lar.2013.29.3.174. Epub 2013 Sep 27.

DOI:10.5625/lar.2013.29.3.174
PMID:24106513
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3791352/
Abstract

Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic nature. Based on these advantages, we sought to develop a new animal model of osteoporosis using micropig, which differs from other miniature pigs in the genetic background. Female micropigs were used for the induction of a moderate osteoporosis model by bilateral ovariectomy (OVX) and compared with shamoperated animals. For osteoporosis evaluation, clinical biomarkers such as blood osteocalcin (OSC) and parathyroid hormone (PTH) levels were measured, as well as bone mineral density (BMD) using micro-computed tomography (micro-CT). Compared to sham, OVX animals have decreased blood OSC level, while the blood PTH level increased in blood sera. In addition, we observed the significantly decreased BMDs of tibia region in OVX animals. Based on these results, we report that the micropig model developed in this study can be used to develop a new and effective medical method for diagnosis and treatment of osteoporosis.

摘要

骨质疏松症是一个公认的主要健康问题,是一种严重的骨骼疾病,因此迫切需要开发更多更新的该疾病动物模型。在用于测试药物疗效的动物模型中,小型猪模型因其与人类高度相似(有效性)而变得有用且有效,特别是在化合物皮下给药的药代动力学、器官的结构和功能、骨骼形态以及整体代谢特性方面。基于这些优势,我们试图利用微型猪开发一种新的骨质疏松症动物模型,该微型猪在基因背景上与其他小型猪不同。使用雌性微型猪通过双侧卵巢切除术(OVX)诱导中度骨质疏松症模型,并与假手术动物进行比较。为了评估骨质疏松症,测量了血液骨钙素(OSC)和甲状旁腺激素(PTH)水平等临床生物标志物,以及使用微型计算机断层扫描(micro-CT)测量骨密度(BMD)。与假手术组相比,OVX动物的血液OSC水平降低,而血清中的血液PTH水平升高。此外,我们观察到OVX动物胫骨区域的骨密度显著降低。基于这些结果,我们报告本研究中开发的微型猪模型可用于开发一种新的、有效的骨质疏松症诊断和治疗医学方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0c4/3791352/a76098a19b4e/lar-29-174-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0c4/3791352/960f866f9368/lar-29-174-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0c4/3791352/a76098a19b4e/lar-29-174-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0c4/3791352/960f866f9368/lar-29-174-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0c4/3791352/a76098a19b4e/lar-29-174-g002.jpg

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本文引用的文献

1
The Change of Bone Metabolism in Ovariectomized Rats : Analyses of MicroCT Scan and Biochemical Markers of Bone Turnover.去卵巢大鼠骨代谢的变化:MicroCT扫描及骨转换生化标志物分析
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Modulation of bone turnover by alfacalcidol and/or alendronate does not prevent glucocorticoid-induced osteoporosis in growing minipigs.阿法骨化醇和/或阿仑膦酸钠对骨转换的调节不能预防生长中的小型猪糖皮质激素诱导的骨质疏松症。
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Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of estrogen deficiency and inflammation.实验性绝经后多关节炎中的骨质疏松症:雌激素缺乏和炎症的相对作用
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