中文摘要：

目的探讨重组人甲状旁腺素rPTH（1—84）对甲状旁腺切除后甲状旁腺素功能减退大鼠模型替代治疗的效果。方法采用手术切除甲状旁腺的方法建立大鼠甲状旁腺功能减退的模型。将30只造模成功大鼠随机分为生理盐水阴性对照组、骨化三醇阳性对照组、rPTH（1—84）20、40、80、160μg/kg组共6组，每组5只，骨化三醇灌胃给药，生理盐水、rPTH（1—84）皮下注射。5只假手术大鼠设为正常对照组。定期内眦静脉取血，提取血清后测定血钙、血磷生化指标。代谢笼收集大鼠12h尿液，测尿钙浓度。给药10周实验结束后，取大鼠双侧股骨和腰椎也～L5，双能X线骨密度仪检测大鼠双侧股骨骨密度和腰椎骨密度。放射免疫方法检测血清骨源性碱性磷酸酶（BALP）浓度。结果通过甲状旁腺切除、血钙磷指标监测，甲状旁腺素功能减退大鼠模型制备成功。rPTH（1—84）80、160wg／kg组均能使血钙、血磷的浓度恢复至正常水平，两组效果差异无统计学意义（P〉0．05），rPTH（1—84）注射各组骨密度均较正常组高（P值均〈0．05），rPTH（1—84）160μg/kg注射组尿钙、血BALP含量高于正常对照组（P〈0．05）。骨化三醇阳性对照组在给药后血钙浓度恢复正常水平，骨密度较正常组升高，但是血磷水平明显高于正常对照组（P〈0．05），尿钙含量均高于其他各组（P值均〈0．05）。阴性对照组与正常对照组股骨骨密度、腰椎骨密度差异无统计学意义（P〉0．05）。结论rPTH（1—84）80、160μg/kg组均可使钙、磷浓度恢复至正常水平，rPTH（1—84）各浓度注射组均能提高骨密度。骨化三醇可以使血钙恢复正常水平、升高骨密度，但不能降低血磷水平，而且使尿钙排出增加。

英文摘要：

Objective To investigate the replacement therapy of rPTH （1-84） （recombinant human parathyroid hormone （1-84）） to hypothyroidism in established rat model. Method Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection （ negative control group） , calcitriol treatment （positive control group） and quadripartite PTH administration with dose of 20, 40, 80 and 160 μg/kg （experimental groups）. Saline and rPTH（1-84） were injected subcutaneously daily. CalcitrJol was garaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10- week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density （ BMD ） of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry （DXA）. The concentration of bone alkaline phosphatase （BALP） in serum was determined by radioimmunoassay. Result The rat model with hypothyroidism was obtained byexcising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH （ 1-84 ） in the dose of 80 or 160 Ixg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses（P 〉0.05）. The BMD in each group of rats with rPTH （ 1-84 ） administration was increased significantly （ P 〈 0. 05 ）. The levels of urinary calcium and serum BALP in rats of maximum rPTH（1-84） injection group （160 μg/kg） were higher than those of normal co