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 stable and inherited idiopathic hypercalciuric rat model to study the mechanism of idiopathic hypercalciuria. Methods Screening serum calcium and phosphorus and male and female Sprague-Dawley rats with normal levels of 1,25 (OH) 2D3 and 24-hour urinary calcium were passaged repeatedly until the offspring showed hypercalciuria. Immunohistochemistry (SP method) was used to detect the expression of vitamin D receptor in small intestine mucosa. Results The 24 h urinary calcium excretion of 93% (14/15) of the seventh generation male and 92% (12/13) female rats were higher than the two standard deviations of the control group (2.56 ± 0.86 (1.12 ± 0.18) mg / d and (2.86 ± 1.16) mg / dvs. (1.15 ± 0.12) mg / d respectively (F = 27.10, P <0.01; F = 21.16, P <0.01) Serum calcium, phosphorus and 1,25- (OH) 2D3 no significant abnormalities (F <2.22, P> 0.05). VDR expression in small intestinal mucosa of model mice was significantly increased (F = 14.23, P <0.01). Conclusion This model rat can be used as an ideal animal model for studying idiopathic hypercalciuria. Overexpression of small intestinal mucosa may be the pathogenesis of idiopathic hypercalciuria.