鞣花酸缓解糖尿病小鼠肾损伤的抗氧化机制研究

Anti-oxidation Mechanism of Ellagic Acid with Renal Protective Effects in Diabetic Mice

目的:考察鞣花酸对糖尿病小鼠肾脏的保护作用及其机制。方法:40只雄性ICR小鼠随机分为正常对照组、模型对照组、厄贝沙坦组(20 mg·kg^(-1))和鞣花酸组(100 mg·kg^(-1)),每组10只。其中模型对照组、厄贝沙坦组和鞣花酸组采用单次腹腔注射链脲霉素(180 mg·kg^(-1))的方法建立糖尿病小鼠模型。注射3周后厄贝沙坦组和鞣花酸组进行给药干预,正常对照组和模型对照组给予生理盐水,灌胃给药,1次/d,连续4周。观察小鼠一般状态、血糖及体质量,肾组织行HE和PAS染色观察肾脏病理形态,测定尿微量白蛋白、血清和尿样中尿素氮、肌酐、血清和肾脏组织中MDA和T-SOD,并计算肾脏指数。结果:模型对照组较正常对照组血糖、24 h尿微量白蛋白、肾脏指数、血肌酐、血尿素氮、MDA明显升高(P<0.01),体质量、尿肌酐、尿素氮、T-SOD明显降低(P<0.01)。与模型对照组相比,鞣花酸组和厄贝沙坦组小鼠的状态明显好转,系膜增生明显缓解,24 h微量白蛋白明显下降(P<0.01),血肌酐明显下降(P<0.05或P<0.01),尿肌酐和T-SOD明显升高(P<0.05或P<0.01),MDA明显降低(P<0.01)。结论:鞣花酸对糖尿病小鼠的肾损伤具有一定的缓解作用,可能与抗氧化机制有关。

Objective： To explore the protective effect of ellagic acid on diabetic nephropathy and its mechanism. Methods： 40 male ICR mice were randomly divided into normal control group, model control group, irbesartan group （20 mg ·kg^-1 ） and ellagic acid group （ 100 mg·kg^-1 ）, each group of 10. In the model control group, irbesartan group and ellagic acid group, a single intraperitoneal injection of streptozotocin （ 180 mg ·kg^-1） was used to establish a diabetic mouse model. After 3 weeks of injection, irbesartan group and ellagic acid group were given drug intervention, and normal control group and model control group were given normal saline, once a day, for 4 weeks. The general state, blood glucose and body mass of mice were observed and renal pathological changes were observed by HE and PAS staining. The Microalbuminuria, serum, urea nitrogen, creatinine, serum, MDA and T-SOD were deter- mined, and the kidney index was calculated. Results： Compared with the normal control group, the blood glucose, 24 h urinary albumin, kidney index, serum creatinine, blood urea nitrogen and MDA of the model control group were significantly increased （P 〈 0.01 ）, and the body weight, urine creatinine, urea nitrogen and T-SOD significantly reduced （P 〈 0.01 ）. Compared with model control group, the condition of ellagic acid group and irbesartan group improved significantly, mesangial proliferation was relieved significantly, and microalbumin decreased significantly at 24 h （ P 〈 0.01 ）. The serum creatinine decreased significantly （ P 〈 0.05 or P 〈 0.01 ）, the levels of creatinine and T-SOD were significantly increased （P 〈0.05 or P 〈0.01 ）, and MDA was significantly decreased （P 〈 0.01 ）. Conclusion： Ellagic acid may alleviate renal injury in diabetic mice and this effect may be related to antioxidant mechanism.