培哚普利对糖尿病大鼠肾脏病变的保护作用

RENAL PROTECTIVE EFFECT OF PERINDOPRIL IN DIABETIC RATS

目的 :探讨培哚普利对糖尿病大鼠肾脏病变的保护作用及其作用机制。方法 :将实验动物分为正常对照组 (C组 )、糖尿病对照组 (D组 )及培哚普利治疗组 (DP组 )。检测各组第 6 ,12周的血糖、血肌酐、尿蛋白、尿肌酐、肾组织中丙二醛 (MDA)、超氧化物歧化酶 (铜锌SOD)、过氧化氢酶 (CAT)和谷胱甘肽过氧化物酶 (GSH-PX)水平 ,以及光镜及电镜观察肾脏组织。结果 :培哚普利治疗组较非治疗组尿蛋白排泄量、血肌酐水平明显下降 (P <0 .0 5 ) ,MDA含量明显降低 ,肾脏的抗氧化酶活性增加 ;光镜、电镜病理改变DP组较D组有所改善。结论 :糖尿病大鼠肾脏的氧化损伤在糖尿病肾病发展中起重要作用 ,而培哚普利可能通过增加肾脏的抗氧化酶活性从而对糖尿病大鼠肾脏起保护作用。

Objective:To investigate the mechanism of perindopril in protecting the renal lesion of diabetic rats.Methods:The following groups of rats were studied: normal control rats, streptozotocin diabetic rats and diabetic rats treated with perindopril(1mg/kg·d). Blood glucose, serum creatinine, 24h-urine protein,lipid peroxidation (MDA) and activities of Cu, Zn-superoxide dismutase (Cu, Zn-SOD),catalase (CAT) and glutathione peroxidase (GSH-PX) in the kidneys of streptozotocin (STZ)-induced diabetic rats were measured after 6 and 12 weeks of treatment. In addition, the renal tissues were observed by light microscopy and electron microscopy. Results:Serum creatinine level, 24h-urine protein of perindopril treated group were significantly lower than those of diabetic untreated group ( P <0.05). Perindopril also decreased malondialdehyde content and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats. Meanwhile, renal pathologic changes in group DP were improved.Conclusion: Oxidative stress plays an important role in the development of diabetic nephropathy and perindopril can protect the kidney of diabetic rats through the possible antioxidative mechanism.