The Study Of Protective Effects Of Simvastatin On Angâ…¡-induced Cadiocyte Injury And It's Mechanism

Objectives:To invsestgiate the influence of Simvastain on AngII-induced production of MDA,SOD,LDH,apoptosis rate,cadiocyte viability and to explore the mechanism.Methods:1,neonatal rat myocardial cells were isolated and primary cultured in vitro. With the adjusted cell concentration of 5.0×106 L-1, the cadiocytes suspension were divided into control group,positive contrast group(containing AngII),simvastatin-treated group.2,Any stimulus were added to control group except DMEM culture meadium.3,In the positive control group cadiocytes were stimulated by ang-II with the concentration of 100umol/l for 48 hours.4,In the simvastatin- treated groups stimulated with Ang-II (100umol/L), simvastatin with concentration of 100nmol/L,1umol/L,10umol/L was added to three different subgroups respectively according to the concentration. The cadiocytes were cultured for 48 hours also.5,The fifth group of neonatal rat myocardial cells were incubated with ang-II(100umol/L),simvastatin(1.0μmol/l) and mevalonate (0.2mmol/l) for 48 hours .6,Cadiocyte viability were measured by MTT ASSAY, SOD Activity and the contents of MDA,LDH were measured by chemical colorimetry assay, and the apoptosis rate was measured by flow cytometry. Results1,After stimulated with ang-II (100umol/l)for 48 hours, the MTT value(p<0.05),SOD activity(p<0.05) of positive group was significantly lower than that of the blank control group, and the apoptosis rate,the contents of MDA,LDH were significantly higher(p<0.05),2,In the simvastatin-treated groups ,the MTT value(p<0.05),SOD activity(p<0.05) were significantly higher in comparison with the positive group.the contents of MDA,LDH and the apoptosis rate were lower.3,In the fifth group, after incubated with ang-II(100umol/L),simvastatin(1.0μmol/l) and mevalonate (0.2mmol/l) for 48 hours ,the MTT valure,apoptosis rate,SOD activity,contents of MDA and LDH had no significant differences with that of positive group(p<0.05).Conclusions:1,Ang-II can damage neonatal rat myocardial cells, decrease the SOD activity and cell viability and increase the contents of MDA,LDH and apoptosis rate.2,Afer treated for 48 hours, Simvastatin lead to increasing of MTT valure and SOD activity and decreasing of contents of MDA,LDH and apoptosis rate decrease .3,The protective effects of simvasatin on AngII-induced myoctyes injury may relate with the synthesis of mevalonate.