依帕司他对糖尿病大鼠肾组织糖化终末产物受体表达的影响

Effect of epalrestat on expression of advanced glycation end-produt receptor in the kidney of diabetic rats

目的通过研究醛糖还原酶抑制剂依帕司他对糖尿病大鼠肾脏糖化终末产物受体(RAGE)表达的影响,探索其肾保护机制。方法30只大鼠随机分为正常对照组(A组)、未处理糖尿病组(B组)和依帕司他治疗组(C组)。12周后测定各组大鼠肾重/体重比、血糖、糖化血红蛋白(HbA1c)、24h尿蛋白定量及血脂改变,并以实时定量逆转录聚合酶链反应(RT-PCR)测定RAGE表达水平。结果B、C组大鼠肾重/体重比、24h尿蛋白定量、肾组织RAGE表达均显著高于A组(P值均<0.05);与B组相比,C组大鼠肾重/体重比、24h尿蛋白定量、肾组织RAGE表达显著下降(P值均<0.05)。结论依帕司他可抑制糖尿病大鼠肾脏肥大,并降低尿蛋白排泄率,这种肾保护作用可能与其抑制RAGE基因表达有关。

Objective To investigate the effects of epalrestat, an aldose reduetase inhibitor, on the expression of receptor for advanced glycation end-produts（RAGE） in diabetic rat kidneys, and to explore its renoprotection mechanisms in diabetic rats. Methods Thirty rats were randomly divided into 3 groups： normal control （group A）, diabetic control （group B） and diabetic plus epalrestat （group C）. Blood glucose, blood lipid, HbA1c, kidney to body weight ratio and urinary protein excretion were measured after 12 weeks. RAGE mRNA level was analyzed using quantitative real time RT-PCR. Results The kidney to body weight ratio, urinary protein excretion and RAGE mRNA in group B were significantly higher than those in group A （all P〈0.05）. The kidney to body weight ratio, urinary protein excretion, and RAGE mRNA in group C were significantly lower than those in group B（all P〈0.05）. Conclusion Epalrestat can prevent renal hypertrophy and decrease urinary protein excretion in diabetic rats, and this renoprotective effects of epalrestat may be related to its inhibitory effect on RAGE expression.