rhPTH(1-34)对大鼠类固醇性骨质疏松治疗作用研究  

Study on Therapeutic Effect of rhPTH(1-34) on Steroid-induced Osteoporosis in Rats

作　　者：孙立[1] 刘芳[1] 齐卫红[1] 范玉明[1] 李波[1] Sun Li, Liu Fang, Qi Weihong, Fan Yuming, Li Bo(National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing 100176, Chin)

机构地区：[1]中国食品药品检定研究院,药物非临床安全评价研究北京市重点实验室,北京100176

出　　处：《中国药事》2018年第3期354-361,共8页Chinese Pharmaceutical Affairs

摘　　要：目的:观察重组人甲状旁腺激素rhPTH(1-34)对大鼠类固醇性骨质疏松的治疗作用。方法:应用皮下注射醋酸泼尼松龙注射液的方法建立类固醇性骨质疏松模型。给予皮下注射5、10、20μg·kg^(-1)·d^(-1) rhPTH(1-34)治疗12w。观察骨组织形态,计量骨密度、骨生物力学和骨代谢相关的血尿生化指标,综合评价rhPTH(1-34)对大鼠类固醇性骨质疏松的治疗效果。结果:皮下注射醋酸泼尼松龙注射液,骨体积和成骨表面显著下降,骨吸收表面显著升高,表明形成了类固醇骨质疏松。不同剂量的rhPTH(1-34)对大鼠股骨骨密度(BMD)均有显著增加。在股骨生物力学特征方面,rhPTH(1-34)中、高剂量组的最大位移(du)显著升高,高剂量组的衰竭功(U)升高;在股骨骨形态计量学方面,不同剂量的rhPTH(1-34)对骨体积均显著升高,矿化沉积率均显著升高,肋骨宽度(O.Th)均显著下降,骨重建时间(δ)均显著缩短等;在血清和尿生化指标方面,不同剂量的rhPTH(1-34)对骨钙素(BGP)均显著升高,尿羟脯氨酸/肌苷均显著下降,中、高剂量组对尿Ca显著下降。结论:rhPTH(1-34)对大鼠类固醇性骨质疏松具有显著的治疗作用。Objective： To investigate the therapeutic effect of Recombinant Human Parathyroid Hormone（1-34） on steroid-induced osteoporosis in rats. Methods： Steroid osteoporosis model was established by subcutaneous injection of prednisolone acetate, and 5, 10, 20 μg·kg^（-1） rhPTH（1-34） was subcutanceously injected once daily for 12 weeks. The morphology of bone, bone mineral density, bone biomechanics and the serum and urine biochemical indexes related to bone metabolism were observed. The therapeutic effect of rhPTH（1-34） on steroid-induced osteoporosis in rats was evaluated comprehensively. Results： Bone volume and osteogenic surface decreased significantly and bone resorption surface increased significantly after the subcutaneous injection of prednisolone acetate, indicating the formation of steroid osteoporosis. Bone mineral density（BMD） significantly increased after the injection of different doses of rhPTH（1-34）. In the field of bone biomechanics, the maximum displacement（du） in middle or high dose groups increased significantly, work to failure（U） in high dose group increased. In the field of bone histomorphometry, the bone volume increased significantly, the mineral appositional rate significantly increased, the osteoid width（O.Th） significantly decreased, and the bone reconstruction time significantly decreased in all dose groups. As far as the serum and urine biochemical indexes were concerned, BGP affected by different doses of rhPTH（1-34） significantly increased, urinary hydroxyproline/inosine significantly decreased in all dose groups. Urine Ca significantly decreased in middle and high dose groups. Conclusion： rhPTH（1-34） had a remarkable therapeutic effect on steroid-induced osteoporosis in rats.

关 键 词：重组人甲状旁腺激素(1-34) 醋酸泼尼松龙 骨质疏松 骨密度 骨生物力学 

分 类 号：R96[医药卫生—药理学]