Sharma Sameer, Anjaneyulu Muragundla, Kulkarni S K, Chopra Kanwaljit
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160-014, India.
Pharmacology. 2006;76(2):69-75. doi: 10.1159/000089720. Epub 2005 Nov 11.
Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.
糖尿病肾病是一种严重的微血管并发症，也是终末期肾病的主要病因之一。多项研究表明，氧化应激增加是糖尿病肾病病因中的一种主要病理生理机制。白藜芦醇是一种存在于红酒中的多酚类植物抗毒素，已知具有强大的抗氧化特性，因此我们旨在研究其对链脲佐菌素（STZ）诱导的糖尿病大鼠肾功能和氧化应激的影响。通过单次腹腔注射STZ（65mg/kg）诱导大鼠患糖尿病。STZ注射4周后，将大鼠分为四组：对照组大鼠、糖尿病大鼠以及从第4周直至第6周分别用白藜芦醇（5mg/kg和10mg/kg，口服）治疗的糖尿病大鼠。在实验结束时，测量尿白蛋白排泄量、尿量、血清肌酐、血尿素氮、肌酐清除率和尿素清除率。在肾匀浆中测量肾氧化应激标志物丙二醛和谷胱甘肽以及抗氧化酶超氧化物歧化酶和过氧化氢酶的水平。与年龄匹配的对照大鼠相比，注射STZ的大鼠血糖显著升高、多尿、蛋白尿且体重下降。6周后，糖尿病大鼠出现肾功能障碍，表现为肌酐清除率和尿素清除率降低以及蛋白尿，同时氧化应激显著增加，这通过脂质过氧化和关键抗氧化酶的活性来确定。白藜芦醇治疗显著减轻了糖尿病大鼠的肾功能障碍和氧化应激。本研究强化了氧化应激在糖尿病肾病中的重要作用，并指出可能的抗氧化机制是白藜芦醇肾脏保护作用的原因。
