Haase P
J Anat. 1975 Feb;119(Pt 1):19-37.
The development of nephrocalcinosis in the rat following intraperitoneal injections of various concentrations of neutral sodium phosphate (pH 7-4) was studied using histology, histochemistry, electron microscopy and quantitative techniques. Daily injections of 0-5 M phosphate consistently produced nephrocalcinosis after 6 days or more. Calcium deposits were at first confined to the basement membranes of proximal tubules; but a longer course of injections, up to 10 days, resulted in additional basement membrane calcification in the outer cortes, and outer medulla, together with intra-luminal casts, often calcified, in the outer medulla and papilla. Calcification was not found in other organs such as liver, lung, heart or aorta. Results from quantitative estimations of total kidney calcium and phosphorus suggested that it was the calcium content which was important to the initiation of nephrocalcinosis. Ultrastructural changes, suggestive of degeneration or alteration in function, were found in mitochondria of proximal tubules in experimental animals before the onset of histologically evident nephrocalcinosis. Later changes, especially to the basal part of proximal tubular cells and their basal laminae, were thought to be consequent upon the mitochondrial changes. It is suggested that the initial renal damage was caused both directly, by a toxic effect of the phosphate load on the kidney and, indirectly, by stimulation of the parathyroid glands as a result of the hypocalcaemia and hyperphosphataemia which followed an injection of phosphate. Daily doses of 1 M phosphate for 3 days produced a type of nephrocalcinosis which was more typical of that reported by previous investigators, who used high doses of phosphate. Twice daily injections of 0-25 M phosphate for 6 days did not induce nephrocalcinosis, whereas 0-375 M phosphate given twice daily for 6 days produced only minimal calcium deposits compared with animals given 0-5 M phosphate once daily for the same period. This may have important clinical implications, since phosphate has been used to control hypercalcaemia of various etiologies.
通过组织学、组织化学、电子显微镜和定量技术，研究了大鼠腹腔注射不同浓度的中性磷酸钠（pH 7.4）后肾钙质沉着症的发展情况。每天注射0.5M磷酸盐，6天或更长时间后持续产生肾钙质沉着症。钙沉积物最初局限于近端小管的基底膜；但注射时间延长至10天，会导致外皮质和外髓质的基底膜额外钙化，同时外髓质和乳头出现管腔内铸型，且常钙化。在肝脏、肺、心脏或主动脉等其他器官中未发现钙化。对肾脏总钙和磷的定量估计结果表明，钙含量对肾钙质沉着症的起始很重要。在组织学上明显的肾钙质沉着症出现之前，实验动物近端小管的线粒体中发现了超微结构变化，提示功能退化或改变。后来的变化，特别是近端小管细胞基部及其基膜的变化，被认为是线粒体变化的结果。有人认为，最初的肾脏损伤是由磷酸盐负荷对肾脏的毒性作用直接引起的，也是由注射磷酸盐后出现的低钙血症和高磷血症刺激甲状旁腺间接引起的。连续3天每天注射1M磷酸盐会产生一种肾钙质沉着症，这更符合之前使用高剂量磷酸盐的研究者所报道的典型情况。每天两次注射0.25M磷酸盐，持续6天不会诱发肾钙质沉着症，而每天两次注射0.375M磷酸盐，持续6天与同期每天一次注射0.5M磷酸盐的动物相比，仅产生极少的钙沉积物。这可能具有重要的临床意义，因为磷酸盐已被用于控制各种病因引起的高钙血症。
