甘草酸对糖尿病大鼠肾脏氧化应激及醛糖还原酶水平的影响

目的:观察甘草酸对糖尿病大鼠肾脏氧化应激及醛糖还原酶活性、基因表达水平的影响,探讨其保护肾脏、预防糖尿病肾病的可能机制。方法:雄性Wistar大鼠30只,随机分为正常对照组、模型对照组和甘草酸治疗组,腹腔注射链脲菌素(60mg/kg)诱导糖尿病模型,治疗组给予甘草酸(30mg/kg/d)治疗16周。16周后测定各组大鼠24h尿白蛋白量(UP24)、肾脏肥大指数(肾重/体重)、丙二醛(MDA)、超氧化物歧化酶(SOD)、醛糖还原酶(AR)活性及mRNA水平。结果:与正常对照组相比,模型组大鼠UP24、肾指数显著升高(P<0.01),血清SOD活性降低,MDA含量增加(P<0.01),肾脏AR活性及基因表达显著升高(P<0.01)。与模型组相比,甘草酸治疗组UP24、肾指数显著降低(P<0.01),血清SOD活性显著增强(P<0.05),同时MDA含量显著减少(P<0.01),肾脏AR活性显著降低、ARmRNA水平显著下降(均P<0.01)。结论:高血糖可诱导机体氧化应激增强、多元醇代谢途径激活及两者的协同效应,促进糖尿病肾病的发生发展;甘草酸可能通过抗氧化应激、减少肾脏AR活性及基因表达以抑制多元醇通路的激活,发挥肾脏保护作用。

Effects of glycyrrhizin on oxidative stress and aldose reductase in rats with diabetic nephropathy

Objective:To investigate the protective effect of glycyrrhizin on renal function and its possible mechanisms in rats with diabetic nephropathy(DN).Methods:Thirty male Wistar rats were randomly divided into normal group,model group and glycyrrhizin group.Diabetes was induced by intraperitoneal injection of streptozotocin(60mg/kg).Glycyrrhizin was given to rats in glycyrrhizin group for 16 weeks(30mg/kg/d).The urinary protein 24-hour(UP24),kidney hypertrophy(kidney weight/body weight),superoxide dismutase(SOD)activity,malondialdehyde(MDA)content in serum,aldose reductase(AR)activity and ARmRNA expression in kidney were measured after the treatment.Results:UP24,kidney hypertrophy,serum MDA content,kidney AR activity and its expression significantly increased,while serum SOD decreased in model group compared with normal group(P<0.01).After treatment of glycyrrhizin for 16 weeks,UP24,kidney hypertrophy,serum MDA content,kidney AR activity and its expression markedly decreased(P<0.01)and serum SOD activity increased(P<0.05)compared with model group.Conclusion:Hyperglycemia can promote the development of diabetic nephropathy by inducing oxidative stress,polyol pathway activation and their synergy effects.Traditional Chinese medicine glycyrrhizin could ameliorate renal dysfunction through reduction of oxidative stress and polyol pathway.