去势大鼠骨质疏松模型药物干预后血清骨酸性磷酸酶5b等骨代谢指标观察

Comparative observation of bone metabolic indices and serum TRACP5b after drug treatment in ovariotomy rats

目的检测切除卵巢大鼠骨质疏松症模型血清中抗酒石酸酸性磷酸酶5b(tartrate-resistantacidphosphataseform5b,TRACP5b)在术后不同时期的变化,结合药物干预及同期测定的脱氧吡啶啉(Dpd)等骨代谢指标、骨组织形态计量学指标变化,探讨TRACP5b对骨质疏松症诊断和疗效监测的意义。方法采用SD雌性大鼠80只,分为5组,每组16只。除假手术组外,均进行大鼠双侧卵巢切除,于术后3d实验组开始给药,术后4、14周取材,进行骨代谢指标及骨组织形态计量学等指标观察。结果大鼠去卵巢4周后,Dpd/肌酐(Cr)与TRACP5b数值模型组明显高于假手术组;14周时TRACP5b值仍高于假手术组。药物干预实验发现,大鼠去势4周,虽然药物干预组与去势组血清E2水平无显著性变化,但Dpd/Cr与TRACP5b指标有显著性变化。实验药物组14周时,骨吸收指标TRACP5b值仍呈极显著性下降,其他骨吸收指标变化差异无显著性。同时骨计量学结果也证实,实验药物组骨体积、骨吸收表面、骨矿化沉积率、骨重建单位时间等指标均得到改善。结论实验证实在骨质疏松症形成的早期(高骨转换期)或晚期(低骨转换期)TRACP5b均能反应破骨细胞活跃程度及骨质疏松症的状态。二膦酸盐与雌激素类药物均有抑制破骨细胞性骨吸收的特点,能降低骨吸收代谢的测定指标。

Objective To investigate the role of bone metabolic indices in the diagnosis and monitoring of therapeutic effects in osteoporosis, the serum tartrate-resistant acid phosphatase form 5b(TRACP5b) level and other parameters such as Dpd in urine of osteoporosis animal model (ovariotomy rats) in different timing point were measured and analyzed. Methods Eighty female SD rats were divided into five groups and had ovariotomy operation (one group was pseudo-operated). Drug treatment began at the third day after the operation. Six rats in each group were sacrificed after 4 weeks and 14 weeks respectively, the bone metabolic indices were measured and bone histomorphometric data were collected. Results Four weeks after operation, the Dpd/Cr and TRACP5b in ovariotomy group were significantly higher than those in the pseudo-operated group, and TRACP5b was still higher after 14 weeks. In the drug treatment groups, serum E2 level was not changed 4 weeks later, however, Dpd/Cr and TRACP5b had changed greatly. After 14 weeks of drug treatment, there was only a significant decrease of TRACP5b among the bone resorption parameters, but other indices had no change.Bone histomorphometric data showed that the bone volume was improved in each drug treatment group. Conclusions Serum TRACP5b level can reflect the activitiy of osteoclasts and the situation of osteoporosis either in the early stage (high turnover period) or in later stage (low turnover period) of osteoporosis. The drugs used in this experiment can inhibit the ostoclast activity and reduce the level of bone resorption parameters, especially the TRACP5b level. Bone histomorphometric results suggestes that the function and manners of different drugs vary in improving of bone volume.