Department of Urology, Wakayama Medical University, Wakayama, Japan.
BJU Int. 2010 Nov;106(10):1550-4. doi: 10.1111/j.1464-410X.2010.09216.x.
To investigate the association between metabolic syndrome and urinary stone disease, and whether insulin resistance associated with adiposity affects the risk of urinary stone formation, using a rat model of metabolic syndrome.
Four-week-old male Otsuka Long-Evans Tokushima 'Fatty' (OLETF, a model of human type 2 diabetes and metabolic syndrome) rats, and Long-Evans Tokushima (LETO, a non-diabetic control) rats (10 each) were given a standardized diet and free access to water. Body weight and serum and urinary biochemistry were determined every 4 weeks. Ten-week-old male OLETF and LETO rats were divided into three groups of nine each and treated with vehicle or oral administration of 3 or 10 mg/kg/day pioglitazone, an agent that improves insulin resistance. After 4 weeks, body weight and serum and urinary biochemistry were determined.
The OLETF rats had significantly lower urinary pH and citrate excretion, and higher urinary uric acid and calcium excretion, than the LETO rats, with increases in body weight, serum triglyceride, glucose and insulin. The administration of pioglitazone to the OLETF rats for 4 weeks significantly increased urinary pH dose-dependently. There was no change in the urinary excretion of citrate, uric acid, calcium, oxalate or magnesium.
These results indicate that metabolic syndrome causes the changes in urinary constituents, leading to increased risk of both uric acid and calcium stone formation. Improvement in insulin resistance, a central cause of metabolic syndrome, might prevent uric acid stone formation by raising urinary pH.
利用代谢综合征大鼠模型，研究代谢综合征与尿石病的关系，以及与肥胖相关的胰岛素抵抗是否会影响尿石形成的风险。
4 周龄雄性 Otsuka Long-Evans Tokushima 'Fatty'（OLETF，一种 2 型糖尿病和代谢综合征的人类模型）大鼠和 Long-Evans Tokushima（LETO，一种非糖尿病对照）大鼠（各 10 只）给予标准饮食，自由饮水。每 4 周测定一次体重和血清及尿液生化指标。10 周龄雄性 OLETF 和 LETO 大鼠分为 3 组，每组 9 只，分别给予 vehicle 或 3 或 10 mg/kg/天吡格列酮（一种改善胰岛素抵抗的药物）口服治疗。4 周后，测定体重和血清及尿液生化指标。
与 LETO 大鼠相比，OLETF 大鼠的尿 pH 值和枸橼酸盐排泄明显降低，而尿尿酸和钙排泄明显升高，体重、血清甘油三酯、葡萄糖和胰岛素水平也升高。4 周吡格列酮治疗可使 OLETF 大鼠尿 pH 值呈剂量依赖性升高，但对枸橼酸盐、尿酸、钙、草酸和镁的尿排泄无影响。
这些结果表明代谢综合征导致尿液成分的变化，增加了尿酸和钙结石形成的风险。代谢综合征的核心原因——胰岛素抵抗的改善可能通过提高尿 pH 值来预防尿酸结石的形成。
