Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792-7375, USA.
J Endourol. 2010 Mar;24(3):355-9. doi: 10.1089/end.2009.0202.
Swine models have proven useful for many different disease processes, especially for urologic research. In this study, we sought to create a model of hyperoxaluria in the adult sow by feeding hydroxyproline (HP). The development of an adult porcine model for calcium oxalate stone disease would represent a significant contribution to stone research as previous animal models have been developed only for rats and baby pigs.
The experiment included a total of 12 multiparous, gestating sows (Large White x Landrace). Sows were randomly allotted to one of the two treatment groups. Treatments involved basal diets that were either control diet (CD) or acidogenic diet (AD). Urine was collected for 6 consecutive days. On days 1 and 2, each sow was fed 2 kg of the assigned basal diet (CD or AD). On days 3, 4, and 5, 200 g of L-hydroxyproline (Wilshire Technologies, Princeton, NJ) was added to each basal diet for all the 12 sows. The HP was evenly mixed with the basal diets before feeding. On day 6, each sow was fed the basal diet originally assigned without HP ( Fig. 1 ). Urine was collected for each entire 24-hour period to control for differences in the diurnal and postprandial variations in the renal handling of oxalate and glycolate.
The addition of HP to the diet increased urinary oxalate excretion. Overall, there was a 192% (CD) and 187% (AD) increase in urinary oxalate between days 1 and 3. The increase peaked on day 3 and gradually returned to baseline by day 6. Student's paired t-test was performed and it confirmed that oxalate on days 3 and 5 was significantly different than baseline (p = 0.009 and p = 0.03, respectively). Urinary glycolate also increased as a result of adding HP to the diet. Overall, there was a 12,340% (CD) and 14,400% (AD) increase in urinary glycolate between days 1 and 3. The increase peaked on day 3 and then declined, although remained more than 10 x greater than baseline at day 6. Student's paired t-test confirmed that glycolate levels on days 3, 5, and 6 were significantly different than baseline (p < 0.001, p = 0.01, and p = 0.03, respectively).
The role of oxalate in the formation of kidney stones cannot be understated. Medical prevention and management of calcium oxalate nephrolithiasis will require a comprehensive understanding of oxalate metabolism in humans. A model for human hyperoxaluria can be reliably created in the adult sow. Such a model is necessary to further our understanding of oxalate metabolism and ultimately aid in the prevention of calcium oxalate calculi.
猪模型已被证明对许多不同的疾病过程非常有用，特别是在泌尿科研究中。在这项研究中，我们试图通过喂食羟脯氨酸（HP）在成年母猪中建立高草酸尿症模型。开发用于草酸钙结石病的成年猪模型将是结石研究的重大贡献，因为以前的动物模型仅针对大鼠和小猪进行了开发。
该实验共包括 12 头经产母猪（大白 x 长白）。母猪被随机分配到两个处理组之一。处理包括基础饮食，分别为对照饮食（CD）或产酸饮食（AD）。连续 6 天收集尿液。第 1 天和第 2 天，每头母猪均喂食 2 公斤指定的基础饮食（CD 或 AD）。第 3、4 和 5 天，将 200 克 L-羟脯氨酸（威尔希尔技术公司，新泽西州普林斯顿）添加到所有 12 头母猪的基础饮食中。HP 在喂食前与基础饮食均匀混合。第 6 天，每头母猪均喂食最初分配的基础饮食，而不添加 HP（图 1）。收集整个 24 小时的尿液，以控制草酸和乙二醇在肾脏处理中的昼夜和餐后变化差异。
饮食中添加 HP 会增加尿草酸排泄。总体而言，第 1 天和第 3 天之间，尿草酸排泄增加了 192%（CD）和 187%（AD）。第 3 天达到峰值，然后逐渐在第 6 天恢复到基线。进行了学生配对 t 检验，证实第 3 天和第 5 天的草酸明显不同于基线（p = 0.009 和 p = 0.03）。添加 HP 到饮食中也会增加尿乙二醇。总体而言，第 1 天和第 3 天之间，尿乙二醇增加了 12340%（CD）和 14400%（AD）。第 3 天达到峰值，然后下降，但在第 6 天仍比基线高 10 倍以上。学生配对 t 检验证实第 3 天、第 5 天和第 6 天的乙二醇水平与基线相比差异显著（p < 0.001、p = 0.01 和 p = 0.03）。
草酸在肾结石形成中的作用不容忽视。钙草酸肾结石的医学预防和管理将需要全面了解人类的草酸代谢。可以在成年母猪中可靠地建立人类高草酸尿症模型。这种模型对于进一步了解草酸代谢和最终有助于预防草酸钙结石是必要的。
