Ethylene Glycol Induced Hyperoxaluria Increases Plasma and Renal Tissue Asymmetrical Dimethylarginine in Rats: A New Pathogenetic Link in Hyperoxaluria Induced Disorders
Ethylene Glycol Induced Hyperoxaluria Increases Plasma and Renal Tissue Asymmetrical Dimethylarginine in Rats: A New Pathogenetic Link in Hyperoxaluria Induced Disorders
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DOI：
10.1016/j.juro.2009.09.076
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发表时间：
2010-02-01
影响因子：
6.6
通讯作者：
Sarica, Kemal
中科院分区：
文献类型：
--
作者：
Aydin, Hasan;Yencilek, Faruk;Sarica, Kemal
目的：肾结石的发病机制至今仍不清楚。有证据表明高尿酸可能影响血管内皮，许多研究将肾结石与动脉粥样硬化联系起来。此外，肾血管内皮细胞调节近端肾小管上皮细胞的功能。我们测定了高尿酸对血浆和组织中不对称二甲基精氨酸水平的影响。第二个目的是确定维拉帕米对不对称二甲基精氨酸的影响。材料和方法：共42只Sprague-Dawley大鼠纳入本研究。1A、1B和1C组用乙二醇诱导高尿酸血症2周。2A、2B和2C组接受乙二醇14天和维拉帕米28天。对照组3只接受蒸馏水，不接受任何特定药物。在24小时，并在研究结束时，血液样本，并在24小时，7和28天的组织病理学evaluation.Results：血浆不对称二甲基精氨酸增加早期高尿酸组（p = 0.0002）。在研究期结束时，该效应得以保留（p = 0.01）。在短期和长期随访中，维拉帕米组的不对称二甲基精氨酸没有增加。与对照组相比，高尿酸在肾组织中诱导了显著的不对称二甲基精氨酸染色模式（p = 0.01）。不对称二甲基精氨酸染色在对照组和维拉帕米groups.Conclusions：增加全身和局部组织不对称二甲基精氨酸可能有助于解释高尿酸引起的疾病，如肾结石和动脉粥样硬化的发病机制。
Purpose: The pathogenesis of kidney stones remains elusive. There is some evidence that hyperoxaluria may effect vascular endothelium and many studies link renal stones to atherosclerosis. Also, renal vascular endothelial cells regulate proximal tubular epithelial cell function. We determined the effect of hyperoxaluria on plasma and tissue levels of asymmetrical dimethylarginine. The secondary aim was to determine the effect of verapamil on asymmetrical dimethylarginine.Materials and Methods: A total of 42 Sprague-Dawley rats were included in the study. In groups 1A, 1B and 1C hyperoxaluria was induced with ethylene glycol for 2 weeks. Groups 2A, 2B and 2C received ethylene glycol for 14 days and verapamil for 28 days. Control group 3 received no specific medication but distilled water. Blood samples were obtained at 24 hours and at study end, and kidney samples were obtained at 24 hours, and 7 and 28 days for histopathological evaluation.Results: Plasma asymmetrical dimethylarginine increased early in the hyperoxaluric group (p = 0.0002). The effect was retained at the end of the study period (p = 0.01). There was no increase in asymmetrical dimethylarginine in the verapamil group on short-term and long-term followup. Hyperoxaluria induced a significantly dense staining pattern in renal tissue asymmetrical dimethylarginine vs controls (p = 0.01). Asymmetrical dimethylarginine staining did not differ in the control and verapamil groups.Conclusions: Increased systemic and local tissue asymmetrical dimethylarginine may help explain the pathogenetic mechanisms of hyperoxaluria induced disorders such as nephrolithiasis and atherosclerosis.