Protective Effects And Mechanisms Of Lovastatin On Vascular Endothelial Dysfunction Induced By Homocysteine Thiolactone

AIM To explore the protective effects and mechanisms of lovastatin on impairment of vascular endothelium function in rats induced by homocysteine thiolactone(HTL).METHODS(1)In vitro experiment:The isolated thoracic aorta rings of rat were prepared according to previous methods.The rings were respectively incubated for 90 min with Krebs-Henseleit solusion(K-H) which contained-different agents including HTL(30mmol/L)alone, lovastatin(40μmol/L)alone,HTL plus lovastatin(10,20 or 40μmol/L), HTI,plus L-NAME(0.01 mmol/L)and l ovastatin(40gmol/L),HTL plus NAC(0.05 mmol/L),HTL plus L-arginine(3 mmol/L),HTL plus SOD (200 U/ml).After 90min,the EDR and non-dependent relaxation of thoracic arteries and biochemical index in tissue of vessels were measured.(2)In vivo experiment,the 42 SD rats were randomly divided into seven groups(n=6),and respectively received a gavage of normal salin contained-different drugs for 8 weeks.After 8 weeks,the rats were sacrificed by exanguinate,thoracic arteries and blood sample were got. EDR and non-dependent relaxation of thoracic arteries and biochemical index in sera were measured.RESULTS(1)Results of the experiments in vitro:An incubation of aortic rings for 90 min with HTL(30 mmol/L)resulted in a significant inhibition of EDR,Simultaneously resulted in increase of MDA concentration,decrease of NO contents and the activity of SOD in aortic tissue,but endothelium-independent relaxation was not affected. Lovastatin(10,20 or 40μmol/L)signifecantly protected EDR,and Lovastatin(40μmol/L)attenuated the decrease of NO content and the activity of SOD as well as elevation of MDA concentration in aortic tissue caused by HTL.L-NAME,a nitric oxide synthase inhibitor,partly blocked the protective effects of lovastatin.The NAC and SOD and L-arginine significantly improved endothelial function and biochemical reference injured by HTL.(2)the experiment in vivo,HTL significantly inhibited EDR and simultaneously combined with decrease of NO level,activity of glutathioneperoxidase and SOD as well as increased the content of MDA in sera,stimulated the activation of NF-κBP65 of vascular endothelium in rats.Lovastatin markedly improved the EDR response,simultaneously inhibited the activation of NF-κBP65 of vascular endothelium,maintained the content of NO,glutathione peroxidase and SOD and decrease of MDA content in sera.HTL and Lovastatin had no effect on endothelium-independent relaxation in rat arteries.There are no significant difference in the lipoprotein serum level among all the groups.CONCLUSION The results in vitro and in vivo demonstrated that Lovastatin could significantly protect from impairment of vascular endothelium function in rats induced by HTL.The mechanism may relate to anti-oxidation effects of lovastatin,not depend on its cholesterollowing manner.