醛糖还原酶抑制剂对大鼠肾脏醛糖还原酶基因表达的影响  

Effect of aldose reductase inhibitor on rat kidney aldose reductase gene expression

作　　者：于德民[1] 刘德敏[1] 刘小慧[1] 孙颖[1] 张捷[1] 

机构地区：[1]天津医科大学代谢病医院,天津300070

出　　处：《天津医科大学学报》2005年第4期519-521,共3页Journal of Tianjin Medical University

基　　金：天津市自然科学基金资助(编号:023611211)

摘　　要：目的:观察醛糖还原酶抑制剂(ARI)依帕司他对大鼠肾脏ARmRNA水平和肾功能相关指标的影响。方法:运用在单侧肾结扎的基础上注射STZ的方法建立大鼠糖尿病肾病模型,给予醛糖还原酶抑制剂依帕司他灌胃4周,RT-PCR的方法检测各组大鼠肾皮质ARmRNA水平,观察依帕司他对ARmRNA是否有影响以及血清和尿液中尿素氮(BUN)、肌酐(Cr)和总蛋白(TP)的变化。结果:给药组大鼠肾脏ARmRNA水平明显高于对照组(P<0.05);给予醛糖还原酶抑制剂依帕司他4周后,低剂量组(L组)、高剂量组(H组)ARmRNA水平低于模型对照组(M组)(P<0.05),但L组和H组之间没有差别(P>0.05)。结论:糖尿病肾病大鼠肾脏ARmRNA水平明显升高,说明AR与糖尿病肾病的发生有关;醛糖还原酶抑制剂依帕司他对糖尿病肾病大鼠肾功能没有影响,但可降低ARmRNA水平。Objective： To investigate the effect of an aldose reductase inhibitor （ARI）-epalrestat on AR mRNA level of rat kidney and renal function. Methods： To establish the diabetic nephropathy animal model by an injection of streptozotocin following unilateral kidney ligation. There are four groups including control group, model group, low dose group and high dose group. Low dose group and high dose group was given aldose reductase inhibitor epalrestat 50 mg/kg and 100 mg/kg respectively by intragastric administration, which last for 4 weeks. The level of AR mRNA of rat kidney was analyzed by quantitatively RT-PCR method and evaluate the effect of epalrestat on AR mRNA level between groups. Results： The level of renal function is significantly different between diabetic nephropathy groups and normal controls, but there is no significant difference between the groups given epalrestat and groups without epalrestat. AR mRNA level in rat kidney of diabetic nephropathy is significantly higher than that in rat kidney of normal controls. After given epalrestat 4 weeks, the level of AR mRNA decrease, but there is no significant difference between low dose groups and high dose groups. Conclusion： Rats with diabetic nephropathy have a significantly higher expression of AR mRNA in kidney than normal controls. Epalrestat have no effect on renal function of rats with diabetic nephropathy, but AR mRNA level decrease after given epalrestat for 4 weeks. Rats rendered diabetic by an injection of streptozocin, following half kidney ligation, are an excellent model of diabetic nephropathy.

关 键 词：醛糖还原酶 醛糖还原酶抑制剂 糖尿病肾病 基因表达 

分 类 号：R965[医药卫生—药理学] Q786[医药卫生—药学]