Study On Atorvastatin Up-regulates The Expression Of PPARs And Inhibits The Aging Of Heart

Objective:1.To investigate the changes of aging rats' heart and the effects of atorvastatin on it.2.To explore the changes of the gene expression of PPARs and inflmammatory factor in myocardium of aging rats and the effects of atorvastatin on it.3.To characterize the role of PPARs pathway in atorvastatin down-regulates the expression of inflammatory factor in myocardum of aging rats.Methods:1.Wistar rats at 20 month old were given atorvastain(10,1mg/kg/d) for 4 month.2.The changes of body weight,blood pressure,thickness of left ventricle wall,TG,TC,LDL-C,HDL-C,lipofuscin,MDA,β-galactosidase,SOD, CAT,collagen,cadiocyte apoptosis were detected.3.The gene expression of IL-1β,TNF-α,MMP-9 were evalulated by RT-PCR and western blot.4.The gene expression of PPARα,PPARβ/δ,PPARγwere evalulated by RT-PCR and western blot.5.Primary cultures of cadiocyte were got from aging rats.Cadiocyte were treated by atorvastatin,GW6471,GSK0660,GW9662.The gene expression of IL-1β,TNF-α,MMP-9 were evalulated by RT-PCR and western blot.Results:1.Compared with young rats,the obvious increase were found in blood pressure,HW/BW,thickness of left ventricle,diameter of cadiocyte,CVF,Ⅰ/Ⅲcollagen ratio,number of apoptosis cadiocyte,TG,TC,LDL-C,β-galactosidase, MDA,lipofuscin(P＜0.01);and obvious decrease were found in SOD,CAT, NOS(P＜0.01).2.There was no difference in diastolic blood pressure between atorvastatin groups and aging group(P＞0.05),systolic blood pressure of high-dose group decreased compared with aging group(P＜0.05).Other targets such as body weight,HW/BW,thickness of left ventricle,diameter of cadiocyte,CVF,Ⅰ/Ⅲcollagen ratio,number of apoptosis cadiocyte,TG,TC,LDL-C,MDA,lipofuscin, β-galactosidase decreased and SOD,CAT,NOS increased in atovastatin group compared with aging rats.The better effection were found in high-dose group.3. The gene expression of IL-1β,TNF-α,MMP-9 in aging rats increased compared with young rats(P＜0.01).The gene expression of IL-1β,TNF-α,MMP-9 in atorvastatin group decreased compared with aging rats.The better effection were found in high-dose group.4.The gene expression of PPARα,PPARβ/δ,PPARγin aging rats decreased compared with young rats(P＜0.01).The gene expression of PPARα,PPARβ/δ,PPARγin atorvastatin group rats increased compared with aging rats.The better effection were also found in high-dose group.5.The gene expression of IL-1β,TNF-α,MMP-9 in atorvastatin group decreased compared with control group(P＜0.01).The gene expression of IL-1β,TNF-α,MMP-9 in PPARs antagonist plus atorvastatin group increased compared with atorvastatin group(P＜0.05).No difference were found between control group and DMSO group(P＞0.05).Conlusion:1.There are significant difference in the senescence associated-target, including the blood pressure,HW/BW,thickness of left ventricle,diameter of cadiocyte,CVF,Ⅰ/Ⅲcollagen ratio,number of apoptosis cadiocyte,TG,TC, LDL-C,MDA,LPS,SOD,CAT,NOS,β-galactosidase between aging and young rats.It can be reverse by atorvastatin treatment.2.The IL-1β,TNF-α,MMP-9 expression in myocardium of aging rats increases compared with young rats and atorvastatin down-regulates it obviously.3.The expression of PPARα,PPARβ/δ, PPARγ,in aging rats decreases remarkably and.atorvastatin up-regulates it obviously.4.Atorvastatin inhibits the expression of inflammatory fator in myocardium of aging rats partly via activation of PPARs signal pathway.