Pioglitazone Hyperlipidemia In Rat Plasma Level Of Pai-1 / Vascular Endothelial Cell Function

Objective To investigate the change of plasminogen activator inhibitor-1(PAI-1)and extent of endothelial dsyfunction in hypercholesterolemia and insulin resistance(IR)before and after treatmeat with pioglitazone(an agonist of peroxisome proliferatr activated receptor).Methods 30 heathy male Wister rats were fed with a normal(Control,n=10)or a high cholesterol(HC,n=20)diet for 12 weeks.6 weeks after,fasting blood glucose,insulin and lipids were measured;to evaluate IR,measure insulin sensitivity index(ISI).being fed a high cholesterol diet,20 HC rats were randomized to receive vehicle(n=10)or pioglitazone(HC±Pio,n=10,oral 10 mg·kg^-1·d^-1)during the remaining 6 weeks.At the end of 12 weeks,the rats were anosthetized,and the thoracic aorta was isolated.EC function was determined by comparing vasorelaxation to Ach(acetylcholine),an EC-dependent vasodilator,and acidified NaNO₂,an EC-independent vasodilator;the plasma levels of PAI-1 were detected by ELISA;the level of Tch,TG,LDL-C in the serum was respectively determined by Cholesterol Kit,Triglycerides Kit and LDL cholesteril Kit and fasting blood glucose,insulin were detected again.Results Compard with normalcontrol group,HC rats had increased level of Tch,TG,LDL fasting blood glucose and insulin obviously(p＜0.05～p＜0.001);ISI was depressed obviously (p＜0.001);and plasma PAI-1 was significantly higher(p＜0.05).IR caused asignificant EC dysfunction(maximal relaxation to Ach:50.51%±2.45%vs 99.78%±3.01%C,p＜0.01) Treatment with pioglitazone depressed obviously level of PAI-1(.p＜0.001)and improved endothelium dependent Vasodilatation.Conclusions our results demonstrated that IR can caused plasma PAI-1 higher and endothelial dysfunction.In addition,pioglitazone may exert asignificant vasoprotective effect in IR rats.