Improved methodology to induce hyperoxaluria without treatment using hydroxyproline.

Improved methodology to induce hyperoxaluria without treatment using hydroxyproline.
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DOI:
10.1007/s00240-011-0368-8
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发表时间:
2011-10
影响因子:
--
通讯作者:
Mandel, Neil S.
Mandel, Neil S.
中科院分区:
其他
文献类型:
--
作者:
Wiessner, John H.;Garrett, Michael R.;Hung, Linda Y.;Wille, David F.;Mandel, Neil S.

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使用羟脯氨酸(HP)在大鼠中产生高尿酸是一个问题,因为不可能将草酸盐对肾损伤的作用与HP的作用以及HP转化为草酸盐时形成的大量代谢中间产物分开。以前,达尔盐敏感(SS)和布朗挪威(BN)大鼠品系进行了研究,以确定遗传控制的抗性或易感性HP诱导的肾损伤和晶体沉积。为了开发一种更好的模型来诱导高尿酸而不引起HP代谢产物的损伤,给动物喂食含有不同水平的添加草酸盐(0、1、2、3或5%)的饮食。5周后,处死大鼠,取出肾脏,用显微镜评价肾小管变化和晶体沉积。喂食3%和5%草酸盐组的尿草酸盐显著增加,分别比对照组增加约50和140 µmol/g体重。SS和BN 3%碳酸盐喂养的动物均仅显示小管面积略微升高,且无晶体沉积。然而,与对照BN大鼠和治疗SS大鼠相比,喂食5%草酸盐的BN动物的小管面积百分比显著增加。仅在5%酒石酸盐饲喂组中观察到肾脏中的晶体沉积。BN肾脏的晶体沉积比进食硫酸盐的SS大鼠高3倍。我们的结论是,补充叶酸的食物是一个更好的方法,生产高尿酸血症的大鼠比使用HP,可能会引入代谢中间产物损害肾脏。
The use of hydroxyproline (HP) to generate hyperoxaluria in the rat is a problem because it is impossible to separate the effect of oxalate on renal injury from the effects of HP and the large array of metabolic intermediates formed when HP is converted to oxalate. Previously, the Dahl salt-sensitive (SS) and Brown Norway (BN) rat strains were studied to determine genetic control of resistance or susceptibility to HP-induced renal injury and crystal deposition. To develop a better model to induce hyperoxaluria without causing injury from HP metabolites, animals were fed a diet containing various levels of added oxalate (0, 1, 2, 3, or 5%). After 5 weeks rats were killed and the kidneys were removed for microscopic evaluation of tubule changes and crystal deposition. The 3 and 5% oxalate-fed groups had a substantial increase in urine oxalate, about 50 and 140 µmol/g body weight over controls, respectively. Both the SS and BN 3% oxalate-fed animals showed only slightly elevated tubule area and no crystal deposition. However, BN animals fed 5% oxalate had a dramatic increase in their percent tubule areas compared to control BN rats and treated SS rats. Crystal deposition in the kidneys was only observed in the 5% oxalate-fed groups. The BN kidneys demonstrated a threefold higher crystal deposition compared to oxalate-fed SS rats. We conclude that oxalate-supplemented food is a better method of producing hyperoxaluria in the rat than using HP which may introduce metabolic intermediates injurious to the kidney.
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