Research On The Expression Of PPARs In The Myocardium Of ApoE-/-mice Of Different Weeks And The Mechanism Of The Statin Intervention

Objective:Recent research has shown that cardiac hypertrophy is fundamental response of cardiac myocytes to various stimuli,which is associated with significantly increased risk of heart failure and malignant arrhythmia. ApoE-/-mice may occur myocardium remodeling with the development of atherosclerosis of coronary artery.Recently,it has been proved that peroxisome peroliferator activated-receptors(PPARs) are involved in prevention of cardiac hypertrophy,and statins exert their effect on up regulation of PPARs in primary cultures of cardiac myocytes.The purposes of this study were:1.to investigate the the dynamic changes in cardiac morphology and myocardial collagen in apoE-deficient(ApoE-/-) mice of different week in cholesterol-fed;2.To investigate the expression of PPARs in the myocardium of ApoE-/-mice of different weeks and the mechanism of the statin intervention.Methods:Thirty six male apoE-deficient mice with eight week age were fed in high cholesterol feed,aged to 16 weeks,were randomized into three groups: twenty four week group(n=12),thirty two week group(n=12),forty week group (n=12),each group were randomized again into two groups:model group(n=6) and simvastatin intervention group(n=6),normal C57BL/6J mice were set as the control group.Serum cholesterol,low-density lipoprotein cholesterol(LDL-C), triglyceride,high-density lipoprotein cholesterol(HDL-C) concentrations were determined.Optical microscopy was adopted to assess the myocardial cells changes.To observe myocardial collagen with Masson dye,image analysis was performed with computer.Collagen specific dyeing and quantitative analysis was identificated by Picric-Sirius Red Polarimetry.Using Western blot,the MMP-9,Cathepsin S,PPARs expression was observed,the mRNA expression of MMP-9,Cathepsin S,PPARs was measured by real time polymerase chain reaction(PCR).Results:1.As compared with the twenty four week group,total cholesterol,MDA, myocardial cells diameter and the content of myocardial collagen of thirty two and forty week group was significantly increased(P＜0.05),NO and SOD was significantly decreased(P＜0.05).2.Diameter of myocardial cell and the content of myocardial collagen were significantly decreased in simvastatin intervention group(P＜0.05),as the level of NO and SOD was significantly increased(P＜0.05).3.Compared with the model group,MMP-9,Cathepsin S expressions were significantly decreased in simvastatin treatment groups of thirty two week group and forty week group(P＜0.05),PPARα,γexpressions were significantly increased in simvastatin treatment groups of thirty two week group and forty week group(P＜0.05).Conclusion:Diameter of myocardial cell and the content of myocardial collagen were significantly increased in apoE-deficient(apoE-/-) mice in cholesterol-fed with the progress of atherosclerosis and antioxidant capacity,simvastatin may reduce cardiac remodeling.