Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto, Japan.
Int J Mol Med. 2011 Nov;28(5):683-7. doi: 10.3892/ijmm.2011.769. Epub 2011 Aug 10.
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.
最近的研究表明，降脂药物在治疗慢性肾脏病（CKD）如糖尿病肾病方面可能具有潜在益处。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在 db/db 小鼠糖尿病肾病中的作用。从 8 周龄开始，将小鼠用含有 0.005%（w/w）匹伐他汀、罗苏伐他汀和普伐他汀的标准饮食喂养 8 周。他汀类药物治疗对 db/db 小鼠的饮食摄入、体重增加、肥胖或血压没有影响。他汀类药物治疗对血浆脂质水平也没有影响。就白蛋白尿的影响而言，匹伐他汀和罗苏伐他汀分别使白蛋白尿排泄减少了 60%和 40%，但普伐他汀没有，表明这两种药物对糖尿病肾病有作用。此外，匹伐他汀和罗苏伐他汀改善了肾小球肥大。所有他汀类药物治疗均改善了胰岛素抵抗。此外，罗苏伐他汀和普伐他汀治疗降低了尿 8-OHdG 水平所衡量的氧化应激，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脏保护作用不一致。总之，我们的数据表明，匹伐他汀和罗苏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。
