The Study On The Effect Of Atorvastatin On CXCR4、VEGF In The Atherosclerotic Plaque In The Rabbit

Objectives:1. TO study the effection of atorvastatin on the serum lipid and CXCR4、VEGF in the atherosclerotic rabbit;2. To oberserve the influence of atorvastatin on the artery intimal hyperplasia and artery atheromatous plaque evolution process CXCR4and VEGF in the atherosclerotic rabbit;3. To explore the concentration-response relationship of atherosclerosis plaque expression of CXCR4and VEGF with atorvastatin, and to explore the interaction in atheromatous plaque formation procession.Methods:20New Zealand rabbits were randomly divided into two groups:control group(n=5, normal diet100g/d); hyper-cholesterol group (n=15, hyper-cholesterol diet100g/d). hyper-cholesterol group was fed for hyper-cholesterol diet4weeks and then catheter-induced abdominal aorta injury was made.15rabbits were randomly divided into three groups: model group (n=5, hyper-cholesterol diet100g/d); high dose group (n=5, hyper-cholesterol diet100g/d and atorvastatin10mg/Kg/d),low dose group (n=5, hyper-cholesterol diet100g/d and atorvastatin5mg/Kg/d), which were fed for12weeks. The serum TC、TG、LDL-C、HDL-C、CXCR4、VEGF were measured by enzyme-linked innunosobent assy(ELISA) at0、6、12weeks. protein quantitative of CXCR4and VEGF were measured by immune organization committee method and Western-Blotting, and the level of CXCR4and VEGF mRNA were detected by real-time reserve transcriptase-polymerase chain reaction(PCR) in Atheromatous plaque at12weekend.Results:1. Serum cholesterol level measure:Compared with the control group, The serum LDL-C、TG、TC were increased significantly (P<0.01) in model group and atorvastatin group at6w and12w. Compared with model group, atorvastatin group cholesterol were decreased significantly (P<0.05), and comparison with low dose atorvastatin group, high dose atorvastatin group decreased obviously (P<0.05). 2. Serum CXCR4、VEGF level:Comparing with control group, the serum CXCR4and VEGF significantly increased in model group and atorvastatin group at6w and12w (P<0.01). Compared with model group, the serum CXCR4and VEGF were downregulate significantly of atorvastatin groups (P<0.05), and comparison with low dose atorvastatin group, hign dose atorvastatin group was decreased significantly (P<0.05).3. Vascular intima organization and pathology observation:There was no cholesterol deposition for abdomina aorta intima with gross specimen. The surface for artery intimal of model group was covered with porcelain white and atheromatous plaque,but statin group with yellow spotted or yellowish-white stripe. After HE dyeing, artery endothelial of control group integrity, single layer close to elastic plate without cholesterol deposition. Model group endothelial proliferation, thickening, there are a large number of macrophage, the lymphocyte infiltration and capillary proliferation of adventitia. neointimal hyperplasia and foam cell were obviously in Statin drug intervention group.4. The CXCR4and VEGF in atherosclerosis plaque:Abdominal aortic intima was dyeid by immunohistochemical, control group without CXCR4and VEGF positive expression. Model group vascular intima significant positive expression. Comparing with high dose atorvastatin group, CXCR4and VEGF of atherosclerosis plaque witn vascular intima expression more positive than low dose atorvastatin group. Western Blotting detection CXCR4and VEGF in atherosclerosis plaque significantly higher (P<0.01). Compared with model group, atorvastatin group decreasing CXCR4and VEGF expression in atherosclerosis plaque. But high dose atorvastatin group decreasing CXCR4and VEGF expression further than low dose atorvastatin group (P<0.05)5. Expression of CXCR4and VEGF mRNA in atherosclerosis plaque:CXCR4and VEGF mRNA in rabbit artery atheromatous plaque of model group and atorvastatin group higher than those in the control group. Comparing with control group, model group and low dose atorvastatin group CXCR4mRNA expression level more significant (P<0.01). Compared with model group, high dose Atorvastatin group decreasing CXCR4and VEGF mRNA more difference (P<0.05). correlation index-0.8714(P<0.05)Conclusions:1. Serum CXCR4and VEGF were improved by high cholesterol diet, with balloon injury abdominal aorta, which can accelerate the occurrence of atherosclerosis in rabbit.2. Expression of CXCR4and VEGF in atherosclerosis plaque have positive role of formation atherosclerosis plaque.3. CXCR4and VEGF were expressed positive correlation in the rabbit atherosclerosis process.4. Atorvastatin can down-regulate CXCR4and VEGF in atheromatous plaque with concentration-response relationship.