间歇皮下注射人甲状旁腺激素不同片段(hPTH_(1-34)及hPTH_(1-84))对去卵巢大鼠股骨及腰椎骨量的影响

Effects of intermittent administration of human parathyroid hormone (hPTH_(1-34) and hPTH_(1-84)) on bone mineral density of femurs and lumbar vertebrae in ovariectomized rats

目的 比较间歇皮下注射人甲状旁腺激素不同片段 (hPTH1 - 34 )及 (hPTH1 - 84 )对完整雌性(Non OVX)大鼠和去卵巢 (OVX)大鼠股骨及腰椎 1- 4骨矿物含量 (BMC)和骨密度 (BMD)的影响。方法 Wistar雌性大鼠 176只 ,分为hPTH1 - 34 和hPTH1 - 84 两大组 (各 80只及 96只 ) ,每大组又各自分 4组 (每组各 2 0只或 2 4只 ) ,分别为 :两组安慰剂组 (未切卵巢及切卵巢 )用安慰剂 (PBS)进行皮下注射 ,每周 3次 ,共 2周 ;两组治疗组 (未切卵巢及切卵巢 )用hPTH1 - 34 或hPTH1 - 84 ,皮下注射 ,每周 3次 ,共 2周。结果 1 卵巢切除术后 3个月大鼠股骨及腰椎1 - 4BMC和BMD明显下降 ;2 两种片段的甲状旁腺激素(hPTH1 - 34 及hPTH1 - 84 )间歇注射均能使Non OVX大鼠和OVX大鼠股骨及腰椎 1- 4BMC和BMD较相应对照组明显升高 ;且腰椎1 - 4较股骨的BMC和BMD升高更明显 ;3 OVX大鼠治疗后股骨及腰椎1 - 4BMC和BMD的升高率较Non OVX大鼠更明显 ;OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平 ;4 hPTH1 - 34 较hPTH1 - 84 更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用 ,尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显 ;hPTH1 - 34

Objective\ The effects of hPTH 1-34 and hPTH 1-84 on bone mineral content (BMC) and density (BMD) of femurs and lumbar vertebrae determined by dual energy x ray absorbtiometry (DEXA) were compared in intact (Non OVX) and ovariectomy (OVX) rats. Methods\ 176 female Wistar rats were divided randomly into hPTH 1-34 (80)and hPTH 1-84 groups(96), and each group was further divided into two control groups and two therapy groups. Control groups were subcutaneously injected with vehicle (PBS), while therapy groups with hPTH 1-34 or hPTH 1-84 , 3 times a week for 2 weeks. Results\ 1.The BMC and BMD were decreased significantly 3 months after ovariectomy. 2. Intermittent administration of either hPTH 1-34 and hPTH 1-84 increased both BMC and BMD in Non OVX and OVX rats compared with control groups; and the increase of BMC and BMD in lumbar vertebrae 1-4 was higher than that in femurs.3. The increased rates of BMC and BMD of femurs and lumbar vertebrae in OVX group were significantly higher than in Non OVX group after hPTH treatment, and the value could return to pre OVX level. 4 .The hPTH 1-34 could induce higher increase in BMC and BMD of femurs than hPTH 1-84 in both Non OVX and OVX rats. Conclusion\ Intermittent subcutaneous administration of hPTH 1-34 and hPTH 1-84 can increas both BMC and BMD in femurs and lumbar vertebrae of rats , especially in lumbar vertebral body mass and in OVX rats. hPTH can reverse bone loss in OVX rats. Furthermore, the effect of hPTH 1-34 on femural bone mass increment is greater than that of hPTH 1-84 .