Department of Internal Medicine, Section of Endocrinology and Metabolism, Yeditepe University Medical Faculty, Istanbul, Turkey.
J Urol. 2010 Feb;183(2):759-64. doi: 10.1016/j.juro.2009.09.076.
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.
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.
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.
Increased systemic and local tissue asymmetrical dimethylarginine may help explain the pathogenetic mechanisms of hyperoxaluria induced disorders such as nephrolithiasis and atherosclerosis.
肾结石的发病机制仍不清楚。有证据表明，高草酸尿可能会影响血管内皮，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。我们测定了高草酸尿对血浆和组织中非对称二甲基精氨酸水平的影响。次要目的是测定维拉帕米对非对称二甲基精氨酸的影响。
本研究共纳入 42 只 Sprague-Dawley 大鼠。在 1A、1B 和 1C 组中，用乙二醇诱导高草酸尿 2 周。2A、2B 和 2C 组接受乙二醇治疗 14 天，维拉帕米治疗 28 天。对照组 3 未接受特殊药物治疗，但给予蒸馏水。在 24 小时和研究结束时采集血样，在 24 小时、7 天和 28 天采集肾组织样本进行组织病理学评估。
高草酸尿组早期血浆非对称二甲基精氨酸增加（p = 0.0002）。研究结束时仍有这种影响（p = 0.01）。在短期和长期随访中，维拉帕米组非对称二甲基精氨酸没有增加。与对照组相比，高草酸尿组肾组织非对称二甲基精氨酸染色明显密集（p = 0.01）。对照组和维拉帕米组的非对称二甲基精氨酸染色无差异。
全身性和局部组织中非对称二甲基精氨酸的增加可能有助于解释高草酸尿引起的肾结石和动脉粥样硬化等疾病的发病机制。
