螺内酯对2型糖尿病大鼠血管PAI-1 mRNA表达的影响

Influence of Spironolactone on the Expression of PAI-1 mRNA in Aorta of Rats with Type 2 Diabetes Mellitus

[目的]4g讨非选择性醛固酮（aldsterone，ALD）受体拮抗剂-螺内酯（spironolactone，SPI）对2型糖尿病（type2diabeticmellitus，T2DM）大鼠血管纤溶酶原激活物抑制剂-1（plasminogenactivatorinhibitor-1，PAI-1）tuRNA的表达的影响。【方法】高脂高糖喂养加小剂量链脲佐菌素（streptozotocin，STz）腹腔注射法建立2型糖尿病大鼠模型，将成膜的T2DM大鼠随机分为糖尿病对照组（DM—C组）和SPI干预组（DM_S组），继续高脂高糖喂养，正常对照组（NC组）大鼠继续给予普通饲料喂养，其中DM—s组每天给予SPI40rag／（kg·d）灌胃，NC纽和DM—c组每天等量蒸馏水灌胃。每2周监测大鼠体重和血糖水平，第16周末处死大鼠，收集血液标本，检测空腹血糖（FBG）、糖化血红蛋白（HbAlC％）、甘油三酯（TG）、胆固醇（TG）、血钾（K’）。用RT—PCR法检测各组大鼠胸主动脉PAI-1mRNA表达。【结果】DM-C组和DM_S组大鼠FBG、HbAlC％、TG均显著高于NC组（P〈0．01），而DM—s组和DM—C组比较差异无统计学意义（P〉0．05）；三组之间的血K’水平比较差异无统计学意义（P〉0．05）；DM—C组和DM—S组大鼠胸主动脉PAI-1mRNA的表达显著高于NC组（P〈0．01），且DM—C组高于DM—s组（P〈0．05）。【结论1SPI能通过下调T2DM大鼠主动脉PAI-1rnRNA的表达而发挥血管保护作用。

[Objective]To explore the influence of nonselective aldosterone（ALD） receptor antagonist-spirono lactone（SPI） on the expression of type-1 plasminogen activator inhibitor（PAI-1） mRNA in rats with type 2 diabe- tes mellitus（T2DM）. [Methods] The model of T2DM rats was established by being fed with high-sucrose-high-fat diet and intraperitoneally injected with low dose streptozotocin（STZ）. Rat models of T2DM were randomly divided into diabetes mellitus control group（group DM-C） and SPI intervention group（group DM-S）. Each rat in group DM-C and DM-S was continuously fed with high-sucrose-high-fat diet. Rats in normal control group（group NC） were fed with routine animal feeds. Group DM-S was treated with SPI 40mg/kg. day via intragastric administra- tion, while group DM-C and NC were treated with corresponding distilled water. Body weight and blood glucose were monitored every two weeks. Rats were sacrificed at the end of 16 weeks, and blood samples were collected. The fasting blood glucose （FBG）, glycosylated hemoglobin A1 c （ HbAI c~ ）, triglyeeride （TG）, total cholesterol （TC） and blood potassium（K＋ ） were measured. RT-PCR was used to determine PAI 1 in aorta of rats in each group. [Results] FBG, HbAlc~ and TG in group DM-C and group DM-S were markedly higher than those in group NC（ P 〈0.01）, but there was no different between group DM-S and DM-C（ P〉0.05）. There was no sig nificant difference in blood K＋ among three groups（ P 〉0.05）. The expression of PAI-1 mRNA in group DM-C and DM-S was significantly higher than that in group NC（ P〈0.01）, and that in group DM-C was higher than that in group DM-S（ P %0.05）. [Conclusion]SPI may play the protective role for vascular endothelium in T2DM rats through down regulating the expression of PAI-1 mRNA.