罗格列酮对2型糖尿病大鼠肾皮质PAI-1表达的影响

Effects of Rosiglitazone on Expressions of Plasminogen Activator Inhibitor-1 in Kidney of Streptozotocin-diabetic Rats

目的研究罗格列酮对2型糖尿病大鼠血糖血脂的影响及肾皮质纤溶酶原激活物抑制物1(PAI-1)表达的作用。方法采用高糖、高脂、高热量饲料喂食2月后予链脲佐菌素腹腔注射建立大鼠2型糖尿病模型。灌胃给药10周,测定血糖、血脂及24h尿蛋白,取肾皮质提取总RNA,应用RT-PCR检测肾皮质中PAI-1 mRNA表达,免疫组化检测肾脏PAI-1蛋白表达。结果罗格列酮能降低血浆血糖、尿蛋白水平,对血脂的影响不明显,三组肾皮质PAI-1 mRNA的相对值分别为0.67±0.03,1.47±0.07,0.83±0.05,相互间有统计学意义。免疫组化显示,糖尿病组肾小球PAI-1明显增强,罗格列酮能降低肾小球PAI-1表达。结论罗格列酮能降低糖尿病大鼠血糖和尿蛋白水平,抑制肾脏PAI-1表达,这种作用可能是罗格列酮治疗效益的重要机制之一。

Objective To investigate the role of rosiglitazone in improving blood lipids and proteinuria in rats with Type 2 diabete, and the effect of rosiglitazone on expressions of plasminogen activator inhibitor-1 in kidney of streptozotocin-diabetic rats. Methods The rats were randomly assigned to following groups： normal control （CON）group, diabetic rat （DM） group, rosiglitazone 2 mg/（kg·d） treatment group（DM ＋ R）. The levels of urinary protein, total cholesterol, triglyceride and renal function change in rats were measured after10 weeks. The mRNA levels of cortical PAI- lwere detected by RT-PCR. The protein expressions of PAI-lin the rat kidney tissues were detected by immunohistochemistry. Results As compared to CON group, the serum sugar, triglyceride, and the urinary protein excretion in DM group increased. The levels of blood sugar, and microalbuminuria decreased significantly after the rosiglitazone treatment. In comparison with normal group, the expression of PAI-1 in diabetic rat markedly increased （P 〈0.05）. In comparison with diabetic rat group, rosiglitazone could significantly decrease the expression of PAI-1 （P 〈 0.05）. Conclusion Rosiglitazone has better effects in improving the blood sugar and proteinuria of streptozotocin-dia- betic rats. The expression of renal cortical PAI-1 is down-regulated by rosiglitazone.