The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism
10.3760/cma.j.issn.1673-0860.2015.12.011
- VernacularTitle:重组人甲状旁腺素rPTH(1-84)对甲状旁腺切除大鼠替代治疗疗效的研究
- Author:
Zhiwei DING
1
;
Tiancheng LI
;
Yuhe LIU
;
Shuifang XIAO
Author Information
1. 100034,北京大学第一医院耳鼻咽喉头颈外科
- Keywords:
Parathyroid hormone;
Hypoparathyroidism;
Hormone replacement therapy;
Bone density;
Alkaline phosphatase
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2015;50(12):1020-1025
- CountryChina
- Language:Chinese
-
Abstract:
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.Calcitriol was gavaged 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 by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently.Administration of rPTH (1-84)in the dose of 80 or 160 μg/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 control group(P ＜ 0.05).The rats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus concentration compared with normal control group(P ＜0.05).The amount of urinary calcium also exceeded the other groups(P ＜ 0.05), but no with significant difference in BMD of bilateral femoral bone and lumbar vertebra between negative control group and normal control group(P ＞0.05).Conclusion Calcium and phosphorus return to normal level by administration of rPTH (1-84)in the dose of 80 μg/kg or 160 μg/kg, with increase in BMD.Calcitriol can return the level of calcium to normal and increase BMD, but can not correspondingly decrease the phosphorus concentration and increase the excretion of calcium in urine.
