普伐他汀对糖尿病大鼠肾脏氧化应激的抑制作用

Inhibitory effects of pravastatin on oxidative stress in kidney of diabetic rats

目的:探讨普伐他汀(pravastatin)对糖尿病大鼠肾脏氧化应激反应的影响及其机制。方法:将SD大鼠随机分为正常对照组(CN)、糖尿病对照组(DM)、普伐他汀治疗组(DM+P)、褪黑素治疗组(DM+M),每组7只。使用链脲佐菌素(STZ)诱导制备糖尿病大鼠模型。治疗组分别予普伐他汀和对照药物褪黑素(Mel)治疗,8周后检测大鼠血及肾组织中各项生化指标及各项抗氧化指标。结果:成功建立大鼠糖尿病模型。与DM组比较,Mel治疗可使24 h尿蛋白量显著降低(P<0.05),DM+P组尿蛋白排泄量降低更为明显(P<0.01);与DM组比较,DM+P组肾重/体质量比值有所下降(P<0.05)。与DM、DM+M相比,普伐他汀处理对糖尿病大鼠血浆MDA含量、红细胞SOD活性变化无明显影响,但可使全血谷胱甘肽过氧化物酶(GSH-Px)活性在8周时明显升高(P<0.01)。普伐他汀和Mel处理均可使糖尿病大鼠肾脏SOD活性、GSH-Px活性明显升高(P<0.05),普伐他汀还可使肾脏MDA含量显著下降(P<0.01)。结论:普伐他汀能明显改善糖尿病大鼠的肾功能,这可能与其抑制糖尿病大鼠肾脏氧化应激反应有关。

Objective：To investigate the effect of pravastatin on oxidative stress and renal function in the kidney of diabetic rats. Methods： SD rats were randomly divided into normal control group（CN）, diabetic control group （DM）, pravastatin treatment group （DM＋P） and melatonin treatment group （DM＋M）. Pravastatin or melatonin was given to streptozocin-induced diabetic rat for 8 weeks, then the general state and renal function of rats were evaluated. The serum and renal intrinsic anti-oxidant enzyme（AOE） activities and lipid peroxide levels were also examined. Results： Diabetic rat model was successfully induced. Compared with DM control group, the urinary protein excretion was lower in DM＋M group （P〈0.05） and DM＋P group （P〈0.01）. Pravastatin also decreased the renal weight/body weight ratio （P〈0.05）. There was no significant difference in serum lipid peroxide levels and superoxide dismutase（SOD） activities between DM＋P group, DM group and DM＋M group, while glutathione peroxidase （GSH-Px） activities increased significantly in DM＋ P group （P〈 0.01）. Pravastatin and melatonin both increaseed the SOD and GSH-Px activities in renal cortex of diabetic rats （P〈0.05） ; pravastatin also reduced the renal lipid peroxide levels （P〈0.01）. Conclusion： Pravastatin can improve renal function in diabetic rats, partly due to its inhibitory effect on oxidative stress in the kidneys of diabetic rats.