高脂血症致大鼠骨质疏松作用研究初探

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (3): 299-303.

高脂血症致大鼠骨质疏松作用研究初探

尤婷婷, 吴铁, 张志平, 邹丽宜, 黄礴

广东医学院药理教研室, 湛江524023, 广东

收稿日期:2006-03-07 修回日期:2006-12-12 出版日期:2007-03-26 发布日期:2020-11-06
通讯作者: 吴铁, 男, 副教授, 研究方向:骨药理、皮肤药理。Tel:0759-2388588-6 E-mail:wutie2@163.com
作者简介:尤婷婷, 女, 硕士, 助教, 研究方向:骨药理。Tel:0759-2388588-4 E-mail:youtingting777@yahoo.com.cn
基金资助:
广东省科技三项基金项目(2003C30501)

Investigation of rat osteoporosis resulting from hyperlipidemia

YOU Ting-ting, WU Tie, ZHANG Zhi-ping, ZOU Li-yi, HUANG Bo

Department of Pharmacology, Guangdong Medical College, Zhanjiang 524023, Guangdong, China

Received:2006-03-07 Revised:2006-12-12 Online:2007-03-26 Published:2020-11-06

摘要/Abstract

摘要： 目的:用脂肪乳剂建立高脂血症大鼠模型, 初步探讨高脂血症对大鼠骨质丢失的影响。方法:SD大鼠18 只, 随机分成普通饲料组(NS 组) 和脂肪乳剂组(HFD 组), 每组9 只, 普通饲料喂养。普通饲料组予蒸馏水按5 mL/kg 灌胃, 脂肪乳剂组予脂肪乳剂按5 mL/kg 灌胃, 每日1 次, 连续20 周。实验结束后心脏取血处死大鼠, 分离血清测TC 、TG 和高密度脂蛋白胆固醇(HDL-c), 用公式计算低密度脂蛋白胆固醇(LDL-c), 并观察胫骨的骨形态学参数变化。结果:长期脂肪乳剂灌喂使大鼠TC 、LDL-c 水平升高和HDL-c 下降(P <0.01), 胫骨上段骨小梁面积百分数、数量、厚度明显下降(P <0.01), 骨小梁分离度增加(P <0.01), 骨量显著丢失, 荧光标记减弱, 骨形成减少, 红骨髓减少, 白骨髓增加。结论:长期脂肪乳剂灌胃建立的高脂血症大鼠有明显的骨质疏松。

关键词: 脂肪乳剂, 高脂血症, 骨质疏松, 大鼠

Abstract: AIM: To establish the hyperlipemic rat model by long-term gastric perfusion of intralipid and investigate the effects of hyperlipidemia on bone.METHODS: Eighteen SD rats were randomly divided into control group (C) and high-fat-diet group (HDF), with 9 rats per group.Rats of C group were treated orally with normal saline, and rats in HDF group were oral gavage of intralipid at dose of 5.0 mL/kg, once a day for 20 weeks. At the end of experiment, their serum levels of lipid were measured.Bone histomorphometric analysis of thighbone was performed in undecalcified sections, and the length and width of ulnar were measured.RESULTS: Compared with the C group, serum TC and low density lipoproteins (LDL) were increased (P <0.01) and high density lipoproteins (HDL) were decreased (P <0.01). Bonehistomorphometric parameters showed a significant bone loss in the model group (P <0.01).CONCLUSION: Bone loss occurs in the hyperlipemic rat model by long term gastric perfusion of intralipid.

Key words: intralipid, hyperlipidemia, osteoporosis, rats

中图分类号:

R965.2

尤婷婷, 吴铁, 张志平, 邹丽宜, 黄礴. 高脂血症致大鼠骨质疏松作用研究初探[J]. 中国临床药理学与治疗学, 2007, 12(3): 299-303.

YOU Ting-ting, WU Tie, ZHANG Zhi-ping, ZOU Li-yi, HUANG Bo. Investigation of rat osteoporosis resulting from hyperlipidemia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(3): 299-303.

参考文献

1 Von der Recke P, HansenMA, Hassager C.The association between low bone mass at the menopause and cardiovascular mortality[J].Am JMed, 1999;106:274-275.
2 Yamaguchi T, Sugimoto T, Yano S, et al.Plasma lipids and osteoporosis in postmenopausal women[J].Endocr J, 2002;49: 211-217.
3 臧晶, 王继峰, 牛建昭, 等.大豆异黄酮类成分对去卵巢大鼠脂质代谢的影响[J].中国药科大学学报, 2004;35:254-258.
4 朱顺星, 孙强, 邵义祥.激素性股骨头无菌性坏死发病机理的实验研究[J].南通医学院学报, 2002;22:373-375.
5 Laroche M, Pouilles JM, Ribot C, et al.Comparison of the bone mineral content of the lower limbs in men with ischaemic athero-sclerotic disease[J].Clin Rheumatol, 1994;13:611-614.
6 Barengolts EI, Berman M, Kukreja SC, et al.Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women [J].Calcif Tissue Int, 1998;62:209-213.
7 Uyama O, Yoshimoto Y, Yamamoto Y, et al.Bone changes and carotid atherosclerosis in postmenopausal women[J].Stroke, 1997;28:1730-1732.
8 Callister TQ, Raggi P, Cooil B, et al.Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography[J].N Engl JMed, 1998;339: 1972-1978.
9 Edwards CJ, Hart DJ, Spector TD.Oral statins and increased bone mineral density in postmenopausal women[J].Lancet, 2000;355:2218-2219.
10 张少芬, 陈方, 吴铁.长期脂肪乳剂灌胃致小鼠高脂血症模型的研究[J].广东医学院报, 2004;22:328-330.
11 Friedewald WT, Levy RI, Fredrickson DS.Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge[J].Clin Chem, 1972; 18:499-502.
12 高莹, 李可基, 唐世英, 等.几种高脂血症动物模型的比较[J].卫生研究, 2002, 31:97-99.
13 张浩军, 张冰, 刘小青, 等.小鼠高尿酸高脂血症复合模型初探[J].北京中医药大学学报, 2001;24:29-30.
14 Mundy G, Garrett R, Harris S, et al.Stimulation of bone formation in vitro and in rodents by stains[J].Science, 1999;286: 1946-1949.
15 Sugiyama M, Kodama T, Konishi K, et al.Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells[J].Biochem Biphys Res Commun, 2000;271:688-699.
16 Ohnaka K, Shimoda S, Nawata H, et al.Pitavastatin enhanced BMP-2 and osteocalcin expression by inhibition of Rho-associated kinase in human osteoblasts[J].Biochem Biophys Res Commun, 2001;287:337-342.

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