Effect Of Simvastatin On Expression Of Carnitine Patmitoyl Transferase-Ⅰ MRNA And Glucose Transporter-4 MRNA In Vascular Smooth Muscle Layer Of Atherosclerotic Rabbits

Objective To investigate the effect of 3-hydroxy-3-methylglutanyl coenzyme A(HMG-CoA)reductase inhibitor simvastatin on the expression level of carnitine palmitoyl transferase-I (CPT-I) mRNA and glucose transporter-4 (GLUT-4) mRNA in vascular smooth muscle layer of atherosclerotic rabbits.Methods A model of hypercholesterolemia(HC) and atherosclerosis was established by high-cholesterol diet . 25 male New Zealand white rabbits were divided randomly into control group (fed with normal diet,n=8),high-cholesterol-diet group (include of 5% peanut oil,5% pork fat,15% egg yolk,0.5% cholesterol,n=9) and simvastatin group(high-cholesterol-diet and then add simvastatin 3 mg/kg·d three weeks later,n=8). At the beginning of the feeding to the end of 9 weeks and 25 weeks,serum total cholestero(lTC),triglyceride (TG) and low-density lipoprotein(LDL) were examined. At the end of 25th week,Histological changes in ascending aorta were studied by H-E-staining and histomorphometric analysis. The expression of CPT-I mRNA and GLUT-4 mRNA in vascular smooth muscle layer of thoracic aorta were evaluated by competive semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results High cholesterol diet induced hypercholesterolemia and AS in rabbits. In high cholesterol-diet group serum TC,TG and LDL levels elevated. Pathomorphology indicated that extensive aortic intimae(I)and intimae add media(I + M)became thickened and the ratio of the area of intimae to media(SI / SM)was increased(P<0.05) in high cholesterol-diet group. Aortic intimal proliferation in high cholesterol-diet group was associated with a marked decrease in CPT-I mRNA expression and increase in GLUT-4 mRNA expression in vascular smooth muscle layer of thoracic aorta. Simvastatin could remarkably lower serum lipid,attenuated artery intimal proliferation and markedly increased the enhanced CPT-I mRNA expression and decreased in GLUT-4 mRNA expression level in vascular smooth muscle layer of high cholesterol -diet rabbits. There were significant differences of CPT-I mRNA expression and GLUT-4 mRNA expression between control group or simvastatin group and high cholesterol-die group (P<0.05).Conclusions These findings indicated that early treatment with simvastatin not only induced a significant regression of arterial lesions of high cholesterol diet rabbits,but also had a crucial inhibited genesis and development of atherosclerosis effect through up-regulation of CPT-I mRNA expression and down-regulation of GLUT-4 mRNA expression in vascular smooth muscle layer .