甲状旁腺素联合降钙素对大鼠骨质疏松的治疗作用

Therapeutic effect of parathyroid hormone and calcitonin on osteoporosis in rats

目的探讨甲状旁腺素联合降钙素对大鼠骨质疏松的影响及其作用机制,为临床治疗提供理论依据。方法 100只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、降钙素组、联合用药组,每组20只,构建去卵巢大鼠骨质疏松动物模型。骨组织骨密度(bone mineral density,BMD)和骨矿物质含量(bone mineral content,BMC)测定,血清E2检测,骨代谢相关生化指标和标志物检测,观察骨形态结构变化。结果去势组较假手术组腰椎和股骨BMD和BMC、股骨最大负荷及血清E2、Ca、P、骨保护素水平均显著降低(P<0. 05),而联合用药组上述指标较去势组均显著增高(P<0. 05)。去势组血清碱性磷酸酶、OC、RANK水平较假手术组均显著升高(P<0. 05),而联合用药组上述指标较去势组均显著降低(P<0. 05)。去势组骨小梁明显减少,排列稀疏错乱,并出现大片断裂现象,大量纤维组织,骨细胞少见;联合用药组骨小梁较多且致密,形态结构较规整,骨细胞排列较整齐,骨连续性好,骨密质较厚且均匀。结论甲状旁腺素联合降钙素通过提高雌激素水平,调节维持骨代谢,提高骨密度和矿物含量,改善生物力学性能,改善骨组织病理形态学,起到抗骨质疏松疗效和骨保护作用。

Objective To investigate the effect of parathyroid hormone combined with calcitonin on osteoporosis and its mechanism of action,and to provide theoretical basis for clinical treatment. Methods One hundred female SD rats were randomly divided into 5 groups: sham operation group,ovariectomized group,parathyroid hormone group,calcitonin group,and combination drug group,with 20 rats in each group. Osteoporosis animal model was constructed by ovariectomy in rats. Bone mineral density(BMD) and bone mineral content(BMC) were determined. Serum E2 and bone metabolism-related biochemical indicators and markers were detected.Bone morphological changes were observed. Results Compared with those in the sham-operated group,BMD and BMC of the lumbar spine and femur,the maximum femoral load,and serum E2,Ca,P,and OPG levels were significantly lower in the ovariectomized group(P < 0. 05). The above-mentioned indicators in the drug combination group were significantly higher than those in the ovariectomized group(P<0. 05).The serum levels of ALP,OC,and RANK in the ovariectomized group were significantly higher than those in the sham-operated group(P< 0. 05),and the above indicators in the combination group were significantly lower than in the ovariectomized group(P< 0. 05). In the ovariectomized group,the trabecular bone was significantly reduced,the arrangement was sparse and disordered,large-scale fracture occurred,and a large amount of fibrous tissue and bone cells were rare. In the combination drug group,there was more and more trabecular bone,the morphological structure was more regular,the bone cells were arranged neatly,the bone continuity was good,and the bone density was thick and uniform. Conclusion Parathyroid hormone combined with calcitonin enhances estrogen levels,regulates bone metabolism,increases BMD and BMC,improves biomechanical properties,improves bone histopathology,and provides anti-osteoporosis and bone protective function.