羟乙膦酸钠对实验性高钙尿症的防治作用及其机制

Therapeutic effects of etidronate on experimental hypercalciuria and its mechanism

目的 :观察骨吸收抑制剂羟乙膦酸钠对实验性高钙尿症的防治作用 ,并探讨其可能机制。 方法 :建立大鼠实验性高钙尿症模型 ,观察羟乙膦酸钠治疗后 2周和 4周的尿钙 ,Ca2 + / Cr,NAG/ Cr,以及肾和十二指肠 Ca2 + - ATP酶 (钙泵 )的变化。结果 :2周时尿钙 ,Ca2 + / Cr,血 AL P虽有所升高 ,但 4周时尿钙 ,Ca2 + / Cr,NAG/ Cr及血 AL P均显著下降 (P<0 .0 1) ,2 4h尿钙定量与尿 NAG/ Cr值呈正相关 ;而靶组织钙泵活性无显著改变。 结论 :骨吸收抑制剂具降尿钙和保肾作用 ,其机制不依赖钙泵活性的改变。

Objective:To observe the therapeutic effects of etidronate (a drug of bone absorption inhibitors) on experimental hypercalciuria and clarify its pharmacological mechanism. Methods:The urine calcium creatinine ratios(Ca 2+ /Cr),24 hours quantitative urinary calcium (UCa 2+ ), N acetyl beta D glucosaminidase creatinine ratios(NAG/Cr) and activity of Ca 2+ ATPase on both kidney and duodenum were measured after 2 and 4 weeks treatment of etidronate in rat models of hypercalciuria established by injection of vitamin D 3. Results: Ca 2+ /Cr, UCa 2+ , NAG/Cr were significantly decreased in rats treated with etidronate at 4th week as compared with rats injected with vitamin D 3, while activity of Ca 2+ ATPase on target tissues were not changed. A marked positive relationship was found between UCa 2+ and NAG/Cr. Conclusion: Etidronate displays a remarkable anticalciuric actions independent of changes of Ca 2+ ATPase on target tissues, suggesting that bone absorption inhibitors could be prescribed into idiopathic hypercalciuria therapy.