The Effects Of Spironolactone On The Expression Of TM And PAI-1in Type2Diabetic Rats

Objective: To investigate the effect of Spironolactone on the expression of TM and PAI-1mRNA in vascular endothelial tissue of type2diabetic rats, and further to evaluate theeffect of nonselective mineralocorticoid receptor(MR) blockade-Spironolactone tovascular tissue and approach its potential mechanism to type2diabetes.Methods: eighty healthy male Sprague-Dawley(SD) rats were divided randomly into2groups:.Normal control rats (Group NC，n=10) were fed with routin animal feeds andexperiment rats(n=70). The model of T2DM rats were established by fed withhigh-sucrose-high-fat diet for8weeks and then injected low dose Streptozotocin(STZ) by30mg/kg. The diabetic rats were divided randomly into two subgroup: diabetes mellituscontrol group(group DM-C,n=11)and diabetic rats treated with Spironolactone (groupDM-S,n-12).The group DM and R rats were fed with the high-sucrose-high-fat diet. Thegroup DM rats were treated with Spironolactone40mg.kg-1.day-1via intragastricadministration while group DM and group NC were treated with corresponding distilledwater for8weeks.Body mass(BM)and peripheral blood glucose of each group were testedevery two weeks.The levels of fasting blood glucose （FBG）、 triglyceride(TG),totalcholesterol(TC), glycosylated hemoglobin (HbA1c)、kalium（K~+）、coagulation were testedat the end of the experiment.The expression levels of TM and PAI-1in thoracic aorta tissueof type2diabetic rats were detected by reverse transcription polymerse chainreaction(RT-PCR).Results:(1) The levels of TC、TG、LDL-C、FBG、HbA1c were significantly higher ingroup DM-C and group DM-S compared with group NC at the end of the experiments(P＜0.01). But there had no statistical differences between DM-C and DM-S groups. Comparedwith NC group, the levels of PT/APTT were significantly higher in group DM-C and groupDM-S;(2) the expressions of TM and PAI-1mRNA in group DM-C and group DM-S groupwere higher than group NC,and the level of PAI-1mRNA in group DM-S was lower thanthat group DM-C(P<0.05)Conclusion: Spironolactone increased tne expression PAI-1-1mRNA,which may represent apotential mechanism for protection against insulin resistence and target organ damage in type2diabetes.