钙敏感受体活性改变对大鼠泌尿系草酸钙结石形成的影响

摘要

Objective To study the changes of CaSR activity on the formation of calcium oxalate stones. Methods A-dult male Sprague Dawley rats were given ethylene glycol and ammonium chloride to induce urolithiasis. Meanwhile, different doses of CaSR inhibitors (NPS-2390) were administered. The values of serum urea, creatinine,P,Ca2+ and Mg2+ ,PTH,24 h urine volume,urine pH,Ca2+ , Mg2+and oxalate were evaluated at the end of the experiment. Kidney sections were examined under a light microscope to study the calcium oxalate crystal deposition, pathological changes and the expression of CaSR. Results The urolithiasis induced by ethylene glycol and ammonium chloride caused not only significant increase of serum ure-a,creatinine, urine oxalate and Ca2+ ,but also great amount of calcium oxalate crystal deposition in kidney. PTH secretion of CaSR inhibitor group increased and blood Ca2+ urine Ca2+ raised. Renal histopathologic examination showed significant increase of calcium oxalate crystals in the kidney tissue of the CaSR inhibitor group,and kidney tissue damage was obvious.Conclusions In the kidney and parathyroid gland the low expression of CaSR can increase the formation of calcium oxalate crystal.%目的 探讨钙敏感受体(CaSR)活性改变对草酸钙结石形成的影响.方法 在实验期间给予乙二醇和氯化铵诱导雄性SD大鼠产生泌尿系草酸钙结石.在造模期间给予不同剂量的CaSR抑制剂(NPS-2390).实验结束时检测各组大鼠血尿素氮(BUN)、肌酐(Cr)、血磷、血钙、血镁、PTH的含量、24 h尿量、尿pH值、尿钙、镁、尿草酸的分泌量,显微镜下观察肾组织切片中草酸钙结晶沉积及病理变化情况及肾脏中CaSR表达情况.从而评价CaSR活性的改变对泌尿系结石形成的影响.结果 成石对照组大鼠血BUN、Cr、尿草酸、尿钙较空白组明显升高并且有大量结晶形成,表明建模成功.CaSR抑制剂组较成石对照组甲状旁腺激素(PTH)的分泌增加并且血Ca2+升高尿钙升高.肾组织病理学检查显示CaSR抑制组的肾脏组织中的草酸钙结晶较成石对照组明显增加,组织病理损伤也较重.结论 肾脏中及甲状旁腺中CaSR的表达下降可以导致草酸钙结晶的形成增加.