Mandel Neil S, Henderson James D, Hung Linda Y, Wille David F, Wiessner John H
Departments of Medicine and Surgery, Medical College of Wisconsin,, Milwaukee, Wisconsin, USA.
J Urol. 2004 Mar;171(3):1301-3. doi: 10.1097/01.ju.0000110101.41653.bb.
The pig has been extensively used in biomedical research because of the similarities in organ structure and function to humans. It is desirable to have an animal model of oxaluria and urolithiasis with physiological, anatomical and nutritional characteristics that more closely resemble those of man. In this study we determined if feeding pigs trans-4-hydroxy-l-proline (HP) increased urine oxalate levels and if it would serve as a model for human hyperoxaluria and stone disease.
Male Yorkshire-Durox cross-bred pigs were fed HP for up to 20 days. Urine was periodically collected and analyzed for oxalate levels and the presence of crystalluria. After 20 days of feeding the kidneys were removed and examined grossly and microscopically for indications of injury, crystal deposition and stone formation.
Feeding pigs 10% HP (weight per weight HP/food) produced hyperoxaluria, which reached a maximum and leveled off by day 6. Urine oxalate remained near this level until the study ended at 20 days regardless of the further increase in HP to 20% of the weight of the food. When the kidneys were removed and grossly examined, calcium oxalate encrustations were observed on multiple papillary tips. Histopathological observation of the papillary tissue showed tissue injury and crystal deposition.
Pigs fed HP have hyperoxaluria and calcium oxalate crystalluria, and calcium oxalate papillary deposits form that may be precursors of kidney stones. The use of the pig as a model of human hyperoxaluria and stone formation should prove ideal for studies of these human diseases.
由于猪的器官结构和功能与人类相似，因此在生物医学研究中得到了广泛应用。人们期望获得一种草酸尿症和尿路结石的动物模型，其生理、解剖和营养特征更接近人类。在本研究中，我们确定给猪喂食反式-4-羟基-L-脯氨酸（HP）是否会增加尿草酸水平，以及它是否可作为人类高草酸尿症和结石病的模型。
雄性约克夏-杜洛克杂交猪喂食HP长达20天。定期收集尿液并分析草酸水平和是否存在结晶尿。喂食20天后，取出肾脏，进行大体和显微镜检查，以观察损伤、晶体沉积和结石形成的迹象。
给猪喂食10%HP（HP重量/食物重量）会导致高草酸尿症，在第6天达到峰值并趋于平稳。无论HP进一步增加至食物重量的20%，尿草酸在研究结束的20天内一直维持在该水平附近。取出肾脏进行大体检查时，在多个乳头尖端观察到草酸钙结痂。乳头组织的组织病理学观察显示组织损伤和晶体沉积。
喂食HP的猪出现高草酸尿症和草酸钙结晶尿，并且形成了草酸钙乳头沉积物，这些沉积物可能是肾结石的前身。将猪用作人类高草酸尿症和结石形成的模型对于这些人类疾病的研究应该是理想的。
