Effects of PPAR-α Ligands on Endothelial Dysfunction in Rats and the Mechanism of Therapy

Objective:To investigate effects of PPAR-α ligands on endothelial dysfunction in hyperlipoidemia rats and the mechanism of fenofibrate therapy.Methods:After weighed,thirty-two male SD rats were divided randomly into four groups: normal diet control group(group A);normal diet+fenofibrate therapy(group B);Hyperlipid diet group(group C) and Hyperlipid diet+fenofibrate therapy group(group D).These animals were weighed at every week and the quantity of animal feeds and drugs was adjusted.After twelve weeks,the blood samples were drawn in order to measure plasma lipids(including TC,TG,LDL-c,HDL-c) and serum NO level.Then the rats were killed,thoracic aortas were taken for observation of vasodilator and vasoconstrictor activity in response and detection NOS.Results:Fenofibrate could remarkably decrease plasma TG level,to a certain extent reduce plasma LDL level,and remarkably increase plasma HDL level.Furthermore,Fenofibrate could evidently increase serum NO and tissular NOS,and observably improve the thoracic artery endothelium-dependent vasodilator activity in response to acetylcholine in vitro.However,the effects of fenofibrate were only partially correlated with changes in plasma lipids and lipoproteins.Conclusion:Fenofibrate can evidently increase serum NO and tissular NOS,and observably improve the thoracic artery endothelium-dependent vasodilator activity in response to acetylcholine in vitro.The effects of fenofibrate may be independent of the decreased of plasma lipids.