Differential effect of statins on diabetic nephropathy in db/db mice
Differential effect of statins on diabetic nephropathy in db/db mice
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DOI：
10.3892/ijmm.2011.769
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
Arai, Hidenori
中科院分区：
文献类型：
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作者：
Tamura, Yukinori;Murayama, Toshinori;Arai, Hidenori
最近的研究表明，降脂药物在治疗慢性肾脏疾病（CKD）（如糖尿病肾病）方面具有潜在的益处。虽然他汀类药物已被广泛用于降低血清胆固醇水平，但这些药物对糖尿病肾病的影响尚未完全阐明。因此，在本研究中，我们研究了不同种类的他汀类药物对db/db小鼠糖尿病肾病的作用。小鼠从8周龄开始以0.005% （w/w）匹伐他汀、瑞舒伐他汀和普伐他汀的标准饲料喂养8周。他汀类药物治疗对db/db小鼠的食物摄入、体重增加、肥胖或血压没有影响。他汀类药物治疗对血脂水平也没有影响。在对尿白蛋白的作用方面，匹伐他汀和瑞舒伐他汀分别使尿白蛋白排泄量减少了60%和40%，而普伐他汀没有，提示这两种药物对糖尿病肾病有作用。此外，匹伐他汀和瑞舒伐他汀可改善肾小球肥大。所有他汀类药物治疗都改善了胰岛素抵抗。此外，瑞舒伐他汀和普伐他汀治疗降低了尿8-OHdG水平测量的氧化应激，而他汀类药物对db/db小鼠肾脏的炎症反应没有影响。这些结果与他汀类药物的肾保护作用不一致。总之，我们的数据表明，匹伐他汀和瑞舒伐他汀可以通过抑制肾小球肥大来改善糖尿病肾病，而不依赖于降脂或抗氧化作用。
Recent studies suggest a potential benefit of the lipid-lowering medication in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although statins have been widely used to lower serum cholesterol levels, the effect of these drugs on diabetic nephropathy has not been fully elucidated. In the present study, therefore, we addressed the role of different kinds of statins on diabetic nephropathy in db/db mice. Mice were fed with a standard diet with 0.005% (w/w) of pitavastatin, rosuvastatin, and pravastatin for 8 weeks starting from 8 weeks of age. The treatment with statins did not affect the food intake, body weight gain, adiposity, or blood pressure in db/db mice. Treatment with statins also had no effect on plasma lipid levels. In terms of the effect on albuminuria, pitavastatin and rosuvastatin reduced the urinary excretion of albumin by 60 and 40%, respectively, but not pravastatin, suggesting the effect of these two drugs on diabetic nephropathy. Furthermore, pitavastatin and rosuvastatin improved glomerular hypertrophy. All statins treatment improved insulin resistance. In addition, rosuvastatin and pravastatin treatment reduced oxidative stress measured by urinary 8-OHdG level, whereas the statins had no effect on the inflammatory response in the kidney of db/db mice. These results are not consistent with the renoprotective effect of statins. In conclusion, our data suggest that pitavastatin and rosuvastatin can improve diabetic nephropathy through the suppression of glomerular hypertrophy, independent of lipid-lowering or anti-oxidative effects.