The Effect Of PDGF On Atrial Fibrosis And The Intervention Of RAS Inhibitors And Statins

BackgroundAtrial fibrillation,heart failure,Rheumatic heart disease, dilated cardiomyopathy are clinically common diseases, which often exist together. These diseases with high morbidity, mortality, lowering the quality of the patients'life, aggravating the patient's economic burden. The study suggests that the mechanisms of the disease have close relationship with atrial fibrosis. At present, the study found these factors such as RAS activation, TGF–β1, inflammation, oxidatie stress, cell apoptosis, CTGF, PDGF, MicRNA cause atrial fibrosis, in recent years, research has found PDGF cause fibrosis in kidney, liver, heart。And PDGF cause atrial fibrosis more easily。but the specific molecular mechanism of PDGF caused atrial fibrosis is still unclear. Many basical and clinical research proof show RAS inhibitors and statins can decrease and prevent atrial fibrosis. It is important to understand the molecular mechanism of atrial fibrosis and to prevent the atrium fibrosis .Objectives:Through the transverse aortic constriction rats caused by atrial fibrosis, understand the role of PDGF in atrial fibrosis,use RAS inhibitors and statins to prevent atrial fibrosis, discusses the intervention of RAS inhibitors and statins on atrial fibrosis for clinical treatment and prevention, and provide a new thinking for cure and prevent atrial fibrosis。Methods:By prepared the transverse aortic constriction rats and caused atrial fibrosis,give regular diet fed, through the random number table divided into SHAM group (group SHAM), the transverse aortic constriction group (group TAC),TAC+ irbesartan group (group IRB,20mg/kg.day), TAC+ simvastatin group (group SIM, 5mg/kg.day), TAC+ irbesartan + simvastatin group (group SIM[5mg/kg.day]+IRB[20mg/kg.day]), each group contains 10 rats, test its left ventricular end diastolic diameter, left ventricular end systolic diameter,interventricular septal,left ventricular posterior wall by 13Mhz detector GE Vingemed ultrasoud.Cutting atrial organization after echocardiogram., test the AngII concentration and the content of PDGF by RIA and ELISA respectively, RT - PCR to detect myocardial hypertrophy markers ANP, fibrosis markers of COL1A1 and PDGF mRNA level expression. Observate the degree of atrial fibrosis and calculate atrial collagen volume fraction with sirius red staining。Results:1.The LVESD,LVEDD,IVS,LVPW of group TAC increased markedly comparing with group SHAM(P<0.01),the LVESD,LVEDD,IVS,LVPW of group TAC are higher than group SIM,IRB,IRB+SIM(P<0.05),compare the group SIM,IRB,IRB+SIM have no difference(P>0.05).2. The AngII concentration and the PDGF protein content of group TAC is higher than that of group SIM,IRB,IRB+SIM( P<0.01) ,group SIM,IRB,IRB+SIM have no significant difference with group SHAM(P<0.05).3. Sirius red staining reveals the red and yellow collagen deposition in atrial muscle tissue, atrial collagen volume fraction results show that group TAC higher than group SIM,IRB,IRB+SIM( P<0.01 ), group SIM,IRB,IRB+SIM have no significant difference with group SHAM(P<0.05),atrial collagen volume fraction of group IRB+SIM is lower than group SIM,IRB(P<0.05).4. Compared with group SHAM,SIM,IRB,IRB+SIM, the mRNA expression of type I collagen, ANP and PDGF of group TAC increased markedly(P<0.01) , group SIM,IRB,IRB+SIM also are higher than group SHAM(P<0.05), the mRNA expression of type I collagen, ANP and PDGF of group IRB+SIM is lower than group SIM,IRB(P<0.05).Conclusions:Through transverse aortic constriction rats compared with intervention group, unused drugs group exist obvious atrial fibrosis, considering that is relative with AngII activation , and AngII activated PDGF may be induced atrial fibrosis is one of the molecular mechanism of atrial fibrosis, ras inhibitors and statins can prevent the activity of AngII for PDGF, combine with statins and ras inhibitors are better than use ras inhibitors and statins respectively.