遗传特发性高钙尿大鼠模型的建立

Establishment of genetic idiopathic hypercalciuric rats model

目的建立能够稳定遗传的特发性高钙尿大鼠模型,初步探讨特发性高钙尿的发生机理。方法筛选血钙、磷及1,25(OH)2D3水平正常而24h尿钙显著升高的雌、雄性SD大鼠,反复繁殖传代,直至子代鼠稳定出现高钙尿。采用免疫组织化学方法(SP法)检测模型鼠小肠黏膜维生素D受体表达情况。结果93%(14/15)的第七代模型雄鼠和92%(12/13)的雌鼠2个24h尿钙排泄值均高于对照组两个标准差以上,分别为(2.56±0.86)mg/dvs.(1.12±0.18)mg/d,(2.86±1.16)mg/dvs.(1.15±0.12)mg/d(F=27.10,P<0.01;F=21.16,P<0.01),而血清中钙、磷及1,25-(OH)2D3无明显异常(F<2.22,P>0.05)。模型鼠小肠黏膜VDR表达显著增强(F=14.23,P<0.01)。结论本模型鼠可作为研究特发性高钙尿症的理想动物模型,小肠黏膜VDR过度表达可能是特发性高钙尿的发病机理。

Objective To establish a colony of genetic idiopathic hypercalciuric rats model which can stablely descend and initially explore the mechanism of idiopathic hypercalciuric development. Methods The male and female rats with the highest 24-h urine Ca excretion and normal serum calcium,phosphorus and 1,25(OH)2D3 were chosen for inbreeding to propagate the colony until the stable hypercalcinuria was achieved in filial generation. Immunohistochemical determination (SP method) was undertaken to determine the VDR expression in model rats duodenum. Results The content of two 24 h urine Ca excretion in 93% male and 92% female generation 7 model rats was double standard deviation more than that in the normal group(2.56±0.86 mg/d vs. 1.12±0.18 mg/d,2.86±1.16 mg/d vs. 1.15±0.12 mg/d respectively)(F=27.10,P*<0.01;F=21.16,P<0.01), while the content of serum calcium,phosphorus and 1,25(OH)2D3 were normal(F<2.22, P>0.05). VDR expression was remarkably increased in model rats duodenum(F=14.23,P<0.01). Conclusions The established genetic idiopathic hypercalciuric rats model is suitable for studying IHU and VDR overexpression may contribute to IHU development.