甲状旁腺激素和骨硬化蛋白抗体联合治疗雌性SD大鼠骨质疏松症的疗效观察

Effect of combined treatment with parathyroid hormone and sclerostin antibody capsules in the treatment of osteoporosis in female SD rats

目的探索甲状旁腺激素(PTH)和骨硬化蛋白抗体(Scl-Ab)联合治疗雌性SD大鼠骨质疏松症的疗效,为临床应用提供实验基础。方法从70只健康雌性SD大鼠随机选取65只行双侧卵巢切除术,其余5只行假手术;术后在正常环境下饲养12周,从双侧卵巢切除大鼠中随机选取5只检测胫骨骨密度,较假手术大鼠下降37.64%,证实骨质疏松大鼠模型建立成功。遂将余下60只双侧卵巢切除大鼠随机分成4组:未用药组15只(其中2只大鼠因伤口感染而死亡)、Scl-Ab组15只(Scl-Ab 25mg/kg皮下注射,2次/周)、PTH组15只(PTH 60μg/kg皮下注射,3次/周)、PTH+Scl-Ab组15只(Scl-Ab 25mg/kg皮下注射,2次/周;同时PTH 60μg/kg皮下注射,3次/周)。治疗12周后处死大鼠取胫骨行Micro-CT、HE组织切片和骨生物力学检测与比较。结果Micro-CT三维重建分析,药物治疗12周后Scl-Ab组、PTH组和PTH+Scl-Ab组骨小梁数量较未用药组明显增多,且骨小梁更粗、联系更为紧密;胫骨干骺端微观参数改善较未用药组更为明显,差异均有统计学意义(均P<0.05),其中PTH+Scl-Ab组最为明显(P<0.05)。HE组织切片可见Scl-Ab组、PTH组和PTH+Scl-Ab组骨小梁之间联系紧密,排列规律,且胫骨干骺端骨量增加,胫骨局部骨组织矿化明显,其中PTH+Scl-Ab组最为明显。骨生物力学检测结果显示Scl-Ab组、PTH组和PTH+Scl-Ab组最大载荷、刚度值均高于未用药组(均P<0.05),其中PTH+Scl-Ab组亦分别高于Scl-Ab组和PTH组(均P<0.05)。结论 PTH、Scl-Ab治疗雌性SD大鼠骨质疏松症的疗效明显,其中两药联用疗效更佳。

Objective To investigate the efficacy of parathyroid hormone（PTH） and sclerostin antibody（Scl- Ab） for treatment of osteoporosis in female SD rats. Methods Female SD rats underwent bilateral ovariectomy（OVX, n=65） or sham- operation（sham, n=5）. Five overiectomized rats were randomly selected and bone mass density（BMD） of tibia was measured to approve the success of osteoporosis model. The remaining overiectomized rats were randomly divided into 4 groups with 15 in each group. PTH（60μg/kg, 3/wk）, Scl- Ab（25mg/kg, 2/wk） and PTH（60μg/kg, 3/wk） plus Scl- Ab（25mg/kg, 2/wk） were injected subcutaneously for 12 wks to rats in PTH, Scl- Ab and PTH＋Scl- Ab groups respectively, no drugs were given to rats in OVX group. The tibial metaphyseals of rats were harvested for evaluation. The results of treatment for osteoporosis were evaluated by micro- computerized tomography（micro- CT）, histological examination and biomechanical measurement.Results Comparison with OVX group, the tibial metaphyseals from groups Scl- Ab, PTH and PTH＋Scl- Ab showed a higher BMD,BV/TV, Tb Th, Tb N, Conn D, maximum load, stiffness and a lower Tb Sp, and the effects were strongest in PTH＋Scl- Ab group.The effect of Scl- Ab or PTH alone was significantly lower than that of combined use in prevention and treatment of osteoporosis of ovariectomized rats. Conclusion The results indicate that Scl- Ab plus PTH had an additive effect on osteoporosis in overiectomized rat.