Experimental induction of calcium oxalate nephrolithiasis in mice.
Experimental induction of calcium oxalate nephrolithiasis in mice.
复制标题
DOI：
10.1016/j.juro.2010.04.065
复制
发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Glenton PA
中科院分区：
文献类型：
--
作者：
Khan SR;Glenton PA
各种转基因和基因敲除小鼠的出现为更好地了解草酸钙 (CaOx) 结石病的病理生理学提供了绝佳的机会。然而，在小鼠体内制造 CaOx 肾结石的尝试并不十分成功。我们假设小鼠 CaOx 肾结石需要增加钙和草酸盐的尿排泄，仅通过实验诱导高草酸尿症是不够的。为了提供证据，我们通过给正常尿钙和高尿钙小鼠施用高草酸尿诱导剂来诱导高草酸尿，并研究了肾结石的各个方面。通过饮食向雄性和雌性正常尿钙 B6 小鼠以及高钙尿 Npt2a −/− 小鼠给予乙二醇 (EG)、乙醛酸 (GOx) 或羟脯氨酸 (HLP)，持续 4 周。在第 0.3、7、14、21 和 28 天收集 24 小时尿液样本，并分析 pH、肌酐、乳酸脱氢 (LDH) 钙和草酸盐。使用光学显微镜检查肾脏。使用光学显微镜和扫描电子显微镜检查尿液中的晶体。接受 HLP 治疗的高钙尿小鼠无法耐受治疗，必须在 28 天前处死。所有接受 EG、GOx 或 HLP 的小鼠均出现高草酸尿并表现出 CaOx 晶体尿。正常或高钙尿症的雌性小鼠均未出现肾脏 CaOx 晶体沉积。所有服用 Gox 的小鼠和一些服用 EG 的小鼠都出现了 CaOx 肾结石。所有小鼠的肾脏均显示上皮损伤。尤其是服用 GOx 的雄性小鼠表现出更多的肾损伤，并且炎症细胞迁移到晶体沉积物周围的间质中。结果证实，仅诱导高草酸尿症不足以治疗小鼠 CaOx 肾结石。还需要高钙尿症。雄性小鼠的肾脏比雌性小鼠的肾脏更容易受到损伤，并且容易受到 CaOx 晶体沉积的影响。也许上皮损伤会促进晶体滞留。因此，小鼠中的氧化钙肾结石具有性别依赖性，并且需要高钙尿症和高草酸尿症。
Availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of calcium oxalate (CaOx) stone disease. However attempts to produce CaOx nephrolithiasis in mice have not been very successful. We have hypothesized that CaOx nephrolithiasis in mice requires increasing the urinary excretion of calcium as well as oxalate and that experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents to normocalciuric as well as hypercalciuric mice and investigated various aspects of nephrolithiasis. Ethylene glycol (EG), glyoxylate (GOx) or hydroxyl proline (HLP) were administered through diet to male and female normocalciuric B6 mice as well as hypercalciuric Npt2a −/− mice for 4 weeks. 24 hour urine samples were collected on 0.3,7,14,21 and 28 days and analyzed for pH, creatinine, lactate dehydrogensae (LDH) calcium and oxalate. Kidneys were examined using light microscopy. Urine was examined for crystals using both light and scanning electron microscopy. Hypercalciuric mice on HLP did not tolerate the treatment and had to be sacrificed before 28 days. All mice receiving EG, GOx or HLP became hyperoxaluric and demonstrated CaOx crystalluria. None of the female mice, normo or hypercalciuric developed renal CaOx crystal deposits. All mice on Gox and some on EG developed CaOx nephrolithiais. Kidneys of all mice showed epithelial injury. Male mice particularly on GOx showed more renal injury and migration of inflammatory cells into the interstitium around the crystal deposits. Results confirm that induction of hyperoxaluria alone is not sufficient for CaOx nephrolithiais in mice. Hypercalciuria is also required. Kidneys of male mice are more prone to injury than those of female mice and are susceptible to CaOx crystal deposition. Perhaps epithelial injury promotes crystal retention. Thus CaOx nephrolithiais in mice is gender dependent and requires both hypercalciuria and hyperoxaluria.
登录
查看更多内容
DOI：
10.1097/01.asn.0000040593.93815.9d
发表时间：
2003-01-01
影响因子：
13.6
作者：
Wesson, JA;Johnson, RJ;Hughes, J
通讯作者：
Hughes, J
DOI：
10.1152/ajprenal.00620.2007
发表时间：
2008-05-01
影响因子：
4.2
作者：
Khan, Saeed R.;Glenton, Patricia A.
通讯作者：
Glenton, Patricia A.
影响因子：
6.6
作者：
Scales, Charles D., Jr.;Curtis, Lesley H.;Preminger, Glenn M.
通讯作者：
Preminger, Glenn M.
影响因子：
6.2
作者：
Okada, Atsushi;Yasui, Takahiro;Kohri, Kenjiro
通讯作者：
Kohri, Kenjiro
影响因子：
6.6
作者：
Pearle, MS;Calhoun, EA;Curhan, GC
通讯作者：
Curhan, GC