重组人甲状旁腺激素_(1-34)对去卵巢大鼠骨质疏松的治疗作用

Therapeutic Effect of Recombinant Human Parathyroid Hormone _(1-34) on Osteoporosis of Ovariectomized Rats △

目的观察重组人甲状旁腺激素(1-34)犤recombinanthumanparathyroidhormone(1-34),rhPTH(1-34)犦对卵巢摘除(ovariectomy,OVX)大鼠骨质疏松的治疗作用。方法选用雌性6月龄SD大鼠100只,80只行双侧卵巢摘除,3个月后诱发骨质疏松模型。rhPTH(1-34)治疗分为5、10、20、40μg/kg剂量组,每组10只,每日皮下注射1次,每周6次。并设OVX+鲑鱼降钙素治疗(15IU/kg,隔日皮下注射1次)和阿伦膦酸钠治疗(10mg/kg,每日灌胃1次)对照组,每组10只。以OVX和手术不摘卵(Sham)组各10只为对照,治疗观察3个月。以骨干重、灰重,骨密度,股骨三点弯曲载荷,腰椎压缩载荷,骨小梁面积、矿化沉积率和血清碱性磷酸酶(alkalinephosphatase,ALP)、钙、磷,尿吡啶啉/肌酐(urinarypyridinoline/creatin,Pyd/Cr)等指标观察rhPTH(1-34)的治疗作用。结果卵巢摘除3个月后血清E2、子宫湿重和骨量、骨生物力学性能较Sham组明显下降,表明OVX大鼠骨质疏松模型建立。rhPTH(1-34)5～40μg/kg剂量治疗组骨量、骨生物力学性能和骨小梁面积、矿化沉积率明显增高,骨病理形态改善,小剂量治疗组血ALP和尿Pyd/Cr值增加。结论rhPTH(1-34)5～40μg/kg每日1次皮下注射对OVX大鼠骨质疏松有明显治疗作用。

Objective To investigate the therapeutic effect of recombinant human parathyroid hormone (1-34) [rhPTH (1-34) ]on osteoporosis of ovariectomized rats.Methods The model of osteoporosis was formed after3months of ovariectomy with6-month age of80rats.Another20rats was control of sham operation.rhPTH (1-34) was subcutaneously injected once daily with5,10,20,40μg/kg for3months.There were10rats in each group.The control of therapy included Salmon Calcitonin to10rats and Alendronate sodium to10rats.The bone weight of dry and ash,bone mineral density,bone biomechanical property,trabecular area,bone mineral deposition and serum alkaline phosphatase,Ca,P and urinary Pyridinoline/creatin (Pyd/Cr)were measured after the end of therapy.Results When administered to animals as a single subcutaneous injection once daily,rhPTH (1-34) increased obviously bone mass,bone biomechanical property and trabecular area,as well as bone deposition compared with the animals of control group.The bone architecture was ultimately improved by rhPTH (1-34) therapy.Conclusions Rats of ovariectomized-induced osteoporosis possess obvious effect of treatment with low dose of rhPTH (1-34) administered once daily.