一种新型人甲状旁腺素相关肽对去卵巢大鼠骨质疏松的治疗作用

 目的 观察一种新型人甲状旁腺素相关肽（ 8L -hPTH ）对去卵巢大鼠骨质疏松的治疗作用。 方法 88 只 3 月龄 SD 健康雌性大鼠其中 64 只行双侧卵巢摘除术 16 只做假手术。 3 个月后各取 8 只测定腰椎及股骨骨密度。将余下的 56 只卵巢摘除大鼠随机分为 7 组每组 8 只，分别为 8L -hPTH 高、中、低剂量治疗组 ( 剂量分别为 20 ， 10 ， 5 μg·kg^-1·d^-1) ； hPTH(1-34) 高、中、低剂量对照组 ( 剂量分别为 20 ， 10 ， 5 μg·kg^-1·d^-1) ；生理盐水组（ 0.5 mL·d^-1 ），各组均为皮下注射。假手术组余下的 8 只以及剩余 8 只未做任何手术的大鼠，给药方式及剂量均同生 理盐水组。连续给药 3 个月后，比较各组大鼠股骨、腰椎骨密度并用扫描电镜观察股骨情况。 结果 双侧卵巢摘除 3 个月后，大鼠腰椎及股骨骨密度均明显低于假手术组 ( P<0.01) ，说明造模成功。给药 3 月后， 8L -hPTH 各治疗组大鼠与生理盐水组相比较，股骨、腰椎骨密度均显著升高 ( P<0.05) ，骨小梁宽度有极显著增加 ( P<0.001) ，效果呈剂量依赖性。 结论 皮下注射 8L -hPTH(5~20 μg·kg^-1·d^-1) 对去卵巢骨质疏松大鼠有明显的治疗作用。

Therapeutic Effect of a Novel Recombinant Human Parathyroid Hormone Related Peptide on Osteoporosis in Ovariectomized Rats

OBJECTIVE To evaluate the therapeutic effect of a novel recombinant human parathyroid hormone related-peptide on ovariectomized rats. METHODS Sixty-four of 88 3-month-old female Sprague-Dawley rats were ovariectomized and 16 received sham operation.Three months later, 8 rats from each group received bone material density (BMD) test. Then the remaining 56 ovariectomized rats were randomly assigned to 7 groups: control group (NS, 0.5 mL normal saline), 8L-hPTH groups (20, 10, 5 μg·kg-1), hPTH(1-34) groups (20, 10, 5 μg·kg-1). Another 8 rats without any operation and sham-operated rats (sham) were treated in the same way as those of group NS. All rats were subcutaneously injected in consecutive days for 3 months. The femoral and lumbar BMD were measured and the femurs were observed by scanning electron microscope after 3-month-therapy. RESULTS Three months later, the femoral and lumbar BMD of ovariectomized rats were significantly decreased, compared with those of sham-operated rats (P<0.01). Furthermore, the femoral and lumbar BMD and trabecular widths of 8L-hPTH therapeutic groups were all increased obviously compared with those of group NS (P<0.05 and P<0.01). CONCLUSION 8L-hPTH is effective in stimulating bone formation and improving skeletal microarchitecture. 8L-hPTH is potentially a effective therapeutical agent on osteoporosis.