骨质疏松动物模型研究进展和展望

doi:10.3969/j.issn.1674-5817.2011.01.016

摘要/Abstract

摘要： 骨质疏松是一类多种病因引起的系统性疾病, 主要危害老年人人群的健康和生活质量。合适的骨质疏松动物模型是研究该疾病的重要基础。本文就一些经典的制作骨质疏松动物模型的方法作简要的回顾, 并对这些模型在实际应用中所发现的不足之处以及相应的改进作一概述, 同时对近几年新建立的制作骨质疏松动物模型的方法进行综述以及对转向大动物模型的趋势进行展望。

关键词: 原发性骨质疏松, 继发性骨质疏松, 动物模型, 进展, 展望

Abstract: Osteoporosis is an important systemic disorder, impairing mainly the health and life quality of the elderly, with a diverse multifactorial etiology. The proper animal models of osteoporosis lay the foundation of sophisticated studies on this disease. Here, we review some typical animal models of osteoporosi and summarize the drawbacks from the previous using experiences and pose the corresponding improvement of these animal models in actual application. Then, we introduce some novel animal models of osteoporosis and take a perspective view of the requisite needs for large animal models of osteoporosis.

Key words: Primary osteoporosis, Secondary osteoporosis, Animal models, Development, Perspect

中图分类号:

Q95-33

乔伟伟, 赵先哲. 骨质疏松动物模型研究进展和展望[J]. 实验动物与比较医学, 2011, 31(1): 73-78.

QIAO Wei-wei, ZHAO Xian-zhe. Perspective Review of Animal Models for Osteoporosis Research[J]. Laboratory Animal and Comparative Medicine, 2011, 31(1): 73-78.

参考文献

[1] Chachra D, Lee JM, Kasra M, et al.Differential effects of ovariectomy on the mechanical properties of cortical and cancellous bones in rat femora and vertevbrase[J]. Biomed Sci Instrum, 2000, 36: 123-128.
[2] Stroup GB, Hoffman SJ, Vasko2Moser JA, et al. Changes in bone turnover following gonadotropin2releasing hormone (GnRH) agonist administration and estrogen treatment in cynomolgus monkeys : a short-term model for evaluation of antiresorptive therapy[J]. Bone, 2001, 28(5):532-537.
[3] Chavassieux P, Garnero P, Duboeuf F, et al.Effects of a new selective estrogen receptor modulator (MDL 103, 323) on cancellous and cortical bone in ovariectomized ewes: a biochemical, histomorphometric, and densitometric study[J]. J Bone Miner Res, 2001, 16(1):89-96.
[4] Hu YJ, Guo SP, Li XH, et al.The effects of rh2GH and estrogen on mandible and femur in ovariectomized rats bone dense and maximum load[J]. Chin J Osteoporos, 2007, 13(2):91-95.
[5] 宫琳, 周延民, 李春艳, 等. 快速建立兔骨质疏松动物模型的方法[J]. 吉林大学学报(医学版), 2008, 34:903-906
[6] 尚庆, 刘宗超, 鲁晓波. 骨质疏松动物模型特点的综述[J]. 中国实用药物, 2008, 13:193-195.
[7] Liu HY, Liu XY.Effects of Moro-sodium Glutamate Administered Neonataly on growth and development of bone in rat[J]. Chin J Osteopoios, 2000, 6(4):10-12.
[8] Liu HY, Liu XY.The effect of hypothalamic arcuate nucleus damaged by monosodium glutamate on skeleton in rat[J]. Chin J Appl Physiol, 2006, 22(3):363-366.
[9] Ma ZC, Wang DF, Qiu ZQ, et al.Advanced in establishment of osteopoiosis model. Zhongguo Linchuang Kangfu, 2004, 8(33):7478-7480.
[10] 刘浩宇, 刘锡仪. 大鼠脑源性骨质疏松动物模型[J]. 中国骨质疏松杂志, 2008, 3:143-147.
[11] Simonet WS, Lacey DL, Dunstan CR, et al.Osteoprotegerin :a novel secreted protein involved in the regulation of bone density[J]. Cell, 1997, 89:309-319.
[12] 郏蓉, 苗懿德. 护骨素基因多态性与原发性骨质疏松的研究进展[J]. 中国骨质疏松杂志, 2006, 12(4):438-441.
[13] Arko B, Prezelj J, Komel R, et al.Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis[J]. J Clin Endocrinol Metab, 2002, 87:4080-4084.
[14] 孙立昊, 刘建民, 赵红燕, 等. 骨保护素基因启动子区单核苷酸多态性与绝经后妇女骨密度的关系[J]. 诊断学理论与实践, 2005, 4:209-212.
[15] Bekker PJ, Holloway D, Nakanishi A, et al.The effect of a single dose of osteoprotegerin in postmenopausal women[J]. J Bone Miner Res, 2001, 16:348-360.
[16] Windahl SH, Vidal O, Andersson G.Increased cortical bone mineral content but unchanged trabecular bone mineral density in female ERβ(-/-)mice[J]. J Clin Invest, 1999, 104(7):895-901.
[17] Aksakal O, Aytan H, Cavkaytar S, et al.Effect of lactation on bone mineral density later in life in Turkish women[J]. Turkish Journal of Medicai Sciences, 2008, 38:329-333.
[18] 支会英, 李恩. 补肾方药对去卵巢大鼠骨质疏松的骨组织ER 表达的影响[J] . 中国中医基础医学杂志, 2001, 7(4):41-44.
[19] 马仲书, 王蕊, 邱明才. 单剂补肾中药防治去卵巢大鼠骨质疏松的骨形态计量学研究[J] . 天津医药, 1999, 27(3):131-134.
[20] 胡金家, 王曼莹.杜仲叶提取物对体外培养的成骨细胞代谢功能调节研究[J] . 中国中医基础医学杂志, 2001, 7(4):48-50.
[21] 张立. 糖尿病并发去卵巢大鼠骨质疏松症动物模型的建立[J]. 长春医学, 2006; 4(4):1-3.
[22] 乔伟伟,许兰文. 营养性骨质疏橙动物模型的实验研究[J]. 营养学报, 1999, 21(2):240-241.
[23] Kubo T, Shiga T, Hashimoto J, et al.Osteoporosis influences the late period of fracture healing in a rat model p repared by ovariectomy and low calcium diet[J]. J Steroid Biochem Moj Bio1, 1999, 68(526 ):197-202.
[24] Turner RT, Evans GL, Zhang M, et al.Effects of parathyroid hormone on bone formation in a rat model for chroinc alcohol abuse, alcoholism[J]. Clin Exp Res, 2001, 25, 667-671.
[25] Wang Y, Cui Q, Wilson H, et al.Alcohol2induced regulation of genes involved in bone marrow cell osteogenesis and adipogenesis, USA[J]. ORS Transaction, 2003, 27:933.
[26] Lill CA, Fluegel AK, Schneider E.Effect of ovariectomy, malnutrition and glucocorticoid application on bone properties in sheep: a pilot study[J]. Osteoporosis International , 2002 , 13(6):480-486.
[27] Ekici H, Sontas BH, Toydemir TSF, et al.The effect of prepubertal ovariohysterectomy on spine mineral density and mineral content of puppies: A preliminary study[J]. Res Vet Sci, 2007, 82:105-09.
[28] Sonne C, Rigét FF, Beck Jensen JE.Does the nutrition profile of vitamins, fatty acids and microelements counteract the negative impact from organohalogen pollutants on bone mineral density in Greenland sledge dogs (Canis familiaris)?[J]. Environ Int, 2008, 34(6):811-820.
[29] Allen MR, Gineyts E, Leeming DJ.Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra[J]. Osteoporos Int. 2008, 19(3):329-337.
[30] Ding M, Cheng L, Bollen P, Schwarz P.Glucocorticoid induced osteopenia in cancellous bone of sheep: validation of large animal model for spine fusion and biomaterial research[J]. Spine (Phila Pa 1976), 2010, 35(4):363-370.
[31] Adachi JD. Glucocorticoid-induced osteoporosis[J]. Osteoporos Int, 2009, Suppl 3:S239-240.
[32] Zarrinkalam MR, Beard H, Schultz CG, et al.Validation of the sheep as a large animal model for the study of vertebral osteoporosis[J]. Eur Spine J. 2009, 18(2):244-253.
[33] Scholz-Ahrens KE, Delling G, Stampa B.Glucocorticosteroid-induced osteoporosis in adult primiparous Göttingen miniature pigs: effects on bone mineral and mineral metabolism[J]. Am J Physiol Endocrinol Metab, 2007, 293(1):E385-395.
[34] Reinwald S, Burr D.Review of nonprimate, large animal models for osteoporosis research[J]. J Bone Miner Res, 2008,23(9):1353-1368.
[35] Turner AS.Animal models of osteoporosis-necessity and limitations[J]. Eur Cell Mater, 2001, 1:66-81.
[36] Lelovas PP, XanthosTT, Thoma SE. The laboratory rat as an animal model for osteoporosis research[J]. Comp Med, 2008, 58(5): 424-430.