Lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.
Lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.
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脂质过氧化并不是高草酸尿大鼠肾损伤的根本原因。
DOI：
10.1111/j.1523-1755.2005.00735.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hatch,Marguerite
中科院分区：
文献类型：
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作者：
Green,MikeL;Freel,RobertW;Hatch,Marguerite
脂质过氧化不是高尿酸大鼠肾损伤的根本原因。背景高尿酸是草酸钙结石病的主要危险因素，肾损伤被认为是一个重要的起始事件。然而，氧化应激、肾小管损伤和高尿酸在肾结石发生发展中的关系尚不清楚，尤其是在动物模型中。在本研究中，我们评估了氧化应激在慢性高尿酸（HYP）和高尿酸诱导的慢性肾功能衰竭（HRF）大鼠模型中与对照大鼠相比的肾小管损伤中的作用。方法尿中的肾小管酶，包括乳酸脱氢酶（LDH）、碱性磷酸酶（AP）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）和α-和μ-谷胱甘肽-S-转移酶（GST）的排泄在四组Sprague-Dawley大鼠中定量α-GST和μ-GST。本研究包括正常对照组、给予乙二醇（HYP）致高尿酸组、单侧肾切除对照组和给予乙二醇（HRF）的单侧肾切除大鼠。过氧化氢酶，超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GP），谷胱甘肽转移酶（GST）在肾皮质的水平进行了测定4周后，通过测量8-异前列腺素在尿中和脂质过氧化氢在肾cortic. ResultsNAG，AP和LDH的尿排泄量升高后2和4周的HYP和HRF组进行了评估。HRF大鼠4周后尿μ-GST水平升高，这是远端小管损伤的标志物。HYP大鼠与对照组α-GST水平相似，HRF大鼠α-GST水平较对照组低。对照组、HYP组和单侧肾切除对照组大鼠肾皮质中过氧化氢酶、SOD、GP和GST水平相似，但4周后HRF组大鼠肾皮质中过氧化氢酶、SOD、GP和GST水平减弱。肾皮质的脂质过氧化氢含量和尿8-异前列烷水平4 weeks.ConclusionEthylene glycol-induced hyperoxia在Sprague-Dawley大鼠伴有enzymuria，这是肾小管损伤的暗示。治疗4周后，HYP大鼠肾皮质的抗氧化能力与对照大鼠相似;然而，在高尿酸诱导的肾衰竭大鼠中，这种能力显著减弱，尽管显著的脂质过氧化不明显。这些结果表明，脂质过氧化不是高尿酸大鼠肾损伤的根本原因。
Lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.BackgroundHyperoxaluria is a major risk factor of calcium oxalate stone disease and renal injury is thought to be a significant initiating event. However, the relationship among oxidative stress, renal tubule injury and hyperoxaluria in the progression of nephrolithiasis is unclear, especially in animal models. In the current study, we assess the role of oxidative stress in renal tubular damage in a rat model of chronic hyperoxaluria (HYP) and chronic renal failure induced by hyperoxaluria (HRF) compared to control rats.MethodsUrinary excretion of renal tubular enzymes, including lactate dehydrogenase (LDH), alkaline phosphatase (AP), N-acetyl-β-D-glucosaminidase (NAG), and α- and μ-glutathione-S-transferase (α-GST and μ-GST, respectively) was quantified in four groups of Sprague-Dawley rats. The study included normal controls, those made hyperoxaluric with ethylene glycol administration (HYP), unilateral nephrectomized controls, and unilateral nephrectomized rats administered ethylene glycol (HRF). Levels of catalase, superoxide dismutase (SOD), glutathione peroxidase (GP), and glutathione transferase (GST) in the renal cortex were measured after 4 weeks and lipid peroxidation was assessed by measuring 8-isoprostane in the urine and lipid hydroperoxide in the renal cortex.ResultsUrinary excretion of NAG, AP, and LDH was elevated after 2 and 4 weeks in the HYP and HRF groups. Urinary levels of μ-GST, a marker of distal tubule damage, were elevated in HRF rats after 4 weeks. α-GST levels were similar between control and HYP rats but were lower in HRF rats. Levels of catalase, SOD, GP, and GST in the renal cortex were similar among control, HYP, and unilateral nephrectomized control rats, but were attenuated in the HRF rats after 4 weeks. Renal cortical content of lipid hydroperoxide and urinary 8-isoprostane levels were similar among all groups after 4 weeks.ConclusionEthylene glycol-induced hyperoxaluria in Sprague-Dawley rats is accompanied by enzymuria, which is suggestive of renal tubular damage. The antioxidant capacity of the renal cortex in HYP rats is similar to that of control rats after 4 weeks of treatment; however, this capacity is significantly attenuated in rats that are in renal failure induced by hyperoxaluria, although significant lipid peroxidation is not evident. These results suggest that lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.