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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
陈欣, 潘月好, 金国华, 楼舒畅
温州医科大学附属义乌医院(义乌市中心医院)骨科
摘要:
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-Ab25mg/kg皮下注射,2次/周)、PTH组15只(PTH60滋g/kg皮下注射,3次/周)、PTH+Scl-Ab组15只(Scl-Ab25mg/kg皮下注射,2次/周;同时PTH60滋g/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。
关键词:  去势大鼠 骨质疏松症 甲状旁腺激素 骨硬化蛋白抗体
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Effect of combined treatment with parathyroid hormone and sclerostin antibody capsules in the treatment of osteoporosis in female SD rats
CHEN Xin, PAN Yuehao, JIN Guohua, LOU Shuchang
Yiwu Hospital of Wenzhou Medical University
Abstract:
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(60滋g/kg, 3/wk), Scl-Ab (25mg/kg, 2/wk) and PTH (60滋g/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.
Key words:  OVX rats Parathyroid hormone Osteoporosis Sclerostin antibody