摘要 目的 探讨钙敏感受体（CaSR）拮抗剂溶钙素对骨密度和骨代谢的影响，为临床骨质疏松症的治疗提供新的思路。 方法 C57BL6雌性小鼠36只，随机分为对照组(A组)、高钙高维生素D饮食组(B组)、溶钙素20 mg/kg灌胃治疗组（C组）、溶钙素50 mg/kg灌胃治疗组(D组)、特立帕肽(PTH(1-34))20 μg/kg皮下注射组(E组)，小鼠分别处理12周后，测定各组小鼠海绵骨、皮质骨、全骨骨密度及骨组织中成骨关键基因如骨钙素（Bglap2）、Runt相关转录因子（Runx2）mRNA的表达，并探讨溶钙素治疗对小鼠血、尿钙的影响。 结果 干预12周后，B、C、D、E组全骨骨密度与A组比较明显升高，差异均有显著性（F=39.82，P＜0.05）；C、D组全骨骨密度水平较B组明显升高，差异有显著性（P＜0.05）；而D组全骨骨密度与E组比较，差异无显著意义(P＞0.05)。溶钙素可上调Bglap2、Runx2 mRNA的表达，改善骨转换，C、D、E组Bglap2、Runx2 mRNA表达量均较A组显著上调，差异有显著性（F=27.96、21.75，P＜0.05）。此外，与钙和维生素D补充和外源性PTH治疗干预组相比，溶钙素对血钙波动的影响较小，差异无显著性(P＞0.05)。溶钙素也可减少尿钙排泄，D组尿钙水平较B、E组显著降低（F= 2.68，P＜0.05）。 结论 溶钙素可促进骨形成、增加骨密度，有可能成为骨质疏松症有效的治疗药物。 Abstract：Objective To determine the effects of calcilytic, an antagonist of the calcium-sensing receptor (CaSR), on bone density and bone metabolism, and to provide new insights into the clinical treatment of osteoporosis. Methods Thirty-six female C57/BL6 mice were randomly divided into control group (group A), high-calcium and high-vitamin D group (group B), intragastric 20 mg/kg calcilytic group (group C), intragastric 50 mg/kg calcilytic group (group D), and subcutaneous 20 μg/kg teriparatide ((PTH)1-34) (group E). The mice were administered the respective treatments for 12 weeks. Cancellous, cortical, and total bone mineral density, and mRNA expression levels of key osteogenic genes in the bone tissue, including osteocalcin (Bglap2) and Runx-related transcription factor (Runx2), were measured to determine the effects of calcilytic treatment on serum and urine calcium levels in mice. Results After 12 weeks of treatment, total bone mineral density was significantly higher in groups B, C, D, and E than in group A (F=39.82,P<0.05). Total bone density was also significantly higher in groups C and D than in group B (P<0.05), but not significantly different between group D and group E (P>0.05). Bglap2 and Runx2 mRNA levels were significantly upregulated in groups C, D and E than in group A (F=27.96,21.75,P<0.05), which suggested that calcilytic increased Bglap2 and Runx2 mRNA expression and improved bone conversion. In addition, calcilytic treatment had minimal effect on serum calcium level, which was not significantly different than the effects of high-calcium and high-vitamin D treatment or exogenous PTH treatment (P>0.05). Urine calcium level was significantly lower in group D than in groups B and E, which demonstrated that calcilytic treatment reduced renal calcium excretion (F=2.68,P<0.05). Conclusion Calcilytic promotes bone formation and increases bone density, and is therefore a promising treatment for osteoporosis
