罗格列酮对糖尿病肾病大鼠肾脏的保护作用

目的 探讨罗格列酮对糖尿病肾病(DN)大鼠肾脏的保护作用.方法 单次腹腔注射链脲佐菌素(STZ)诱导糖尿病大鼠模型,将糖尿病大鼠随机分为糖尿病肾病组(DN组,6只)和罗格列酮组(R组,8只),以正常大鼠(N组,6只)作对照.干预8周后,观察各组大鼠尿蛋白、血糖、血脂、血尿素氮(BUN)、血肌酐(SCr)变化;用免疫组化及实时荧光定量PCR分析肾脏环氧化酶-2(COX-2)、过氧化物酶增殖体激活受体γ(PPARγ)的表达.结果 DN组尿蛋白、BUN、SCr、肾脏COX-2蛋白及mRNA水平均较N组明显升高,PPARγ蛋白表达下调;而R组大鼠上述各项检测指标明显逆转;24-h尿蛋白定量分别与COX-2蛋白及mRNA水平呈显著正相关.DN组血糖、血脂均显著高于N组,罗格列酮治疗后上述指标无明显变化.结论 罗格列酮可能通过PPAR途径下调DN大鼠肾脏COX-2表达,发挥不依赖糖脂代谢的直接肾保护作用.

Renoprotective effect of rosiglitazone in rats with diabetic nephropathy

Objective To explore the renoprotective effect of rosiglitazone on the kidneys of rats with diabetic nephropathy (DN). Methods Diabetic model was established by a single injection of streptozotocin(STZ). Diabetic rats were randomly divided into 2 groups of untreated DN group (group DN,n=6) and rosiglitazone-treated DN group (group R,n=8). Six normal rats were taken as the normal controls (group N). Eight weeks later, the excretion of urine protein, blood glucose, serum lipid profile,blood urea nitrogen (BUN) and serum creatinine (SCr) were detected. The expressions of cyclooxygenase-2(COX-2) and peroxisome proliferator-activated receptor γ(PPARγ) were analyzed by immunohistochemistry and real-time Q-PCR. Results Compared with group N, the excretion of urine protein, BUN, SCr and COX-2 expression in group DN were significantly increased, and PPARγ expression was significantly decreased, which were all reversed by the treatment of rosiglitazone in group DN. The levels of COX-2 protein and mRNA were positively correlated with 24-h urine protein excretion. Although blood glucose and serum lipid profile were significantly changed in group DN compared with group N, no significant change occurred following rosiglitazone treatment. Conclusion Rosiglitazone may down-regulate the expression of COX-2 in the kidney of DN rats through PPAR pathway showing non-glucose and lipid metabolism-depenAent renoprotective effect.