The Effects Of Simvastatin On Cardiac Myocytes Inflammation Induced By High Density Glucose And Its Underlying Mechanism

Objectives:1. To objective the influence of high density glucose on cardiac myocytes and investigate its mechanism.2. To objective the effects of simvastatin on the expression of the cardiac myocytes inflammatory factor induced by high density glucose and investigate its underlying mechanism.Methods:1. Cardiac myocytes of SD neonate rats were cultured in vitro.2. Blank control group: there is No stimulant was given to the cardiac myocytes in the blank control group except the DMEM culture fluid, and to cultivate for 72 hours.3. Positive control group: SD neonate rat cardiac myocytes were cultivated with high density glucose (25mmol/L) for 72 hours.4. Mevalonic acid group (MVA): SD neonate rat cardiac myocytes were cultivated with high density glucose (25mmol/L) and mevalonic acid (200umol/L) for 72 hours.5. Simvastatin intervened groups(Sim): different density of simvastatin(10-5mol/L,10-6mol/L,10-7mol/L) was added to three different groups according to the concentration and used to incubate neonate rat cadiocyte for 72 hours while stimulated by high density glucose(25mmol/L).6. Simvastatin and mevalonic acid intervened group(Sim+MVA): SD neonate rat cardiac myocytes were cultivated with simvastatin(10-5mol/L), mevalonic acid (200umol/L) and high density glucose (25mmol/L) for 72 hours.7. The vigor of cadiocytes was detected by MTT chromatometry, inflammatory factor such as TNF-α,ICAM-1,MCP-1 were measured by ELISA, expression of AT1R mRNA and AT2R mRNA in cardiac myocytes were measured by RT-PCR. Results:1. Comparing to the blank control group, the positive group and the MVA group on the vigor of cadiocytes detected by MTT chromatometry were significantly lower (P<0.01), while on TNF-α, ICAM-1 and MCP-1 measured by ELISA were significantly higher (P<0.01).2. MTT chromatometry showed the cadiocytes vigor was increased in the Sim group including the Sim(10-7mol/L) group, the Sim(10-6mol/L) group and the Sim(10-5mol/L) group in a dose- dependent manner (P<0.01) comparing to the positive group, while ELISA showed high density glucose induced TNF-α, ICAM-1 and MCP-1 expression was attenuated by simvastatin in a dose-dependent manner (P<0.05 or P<0.01). There was no significant difference between the Sim+MVA group and the positive group.3. Simvastatin inhibited the increase of the expression of AT1R mRNA measured by RT-PCR in cadiocytes and up regulated the expression of AT2R mRNA in a dose-dependent manner. The Sim(10-5mol/L) group and Sim(10-6mol/L) group on the AT1R mRNA expression were significantly higher (P<0.05) than the positive group while on the AT2R mRNA expression were significantly lower (P<0.05).4. Between AT1R mRNA expression of Cardiac Myocytes and TNF-αconcentration had the positive correlation (coefficient correlation0.701, P<0.01). Between the ratios of AT1R mRNA/AT2R mRNA and the TNF-αconcentration also had the positive correlation (coefficient correlation0.749, P<0.01).Conclusions:1. High density glucose could induce cardiac myocytes inflammation, and injury the cardiac myocytes.2. Simvastatin could suppress the injury and inflammation of cardiac myocytes induced by high density glucose.3. The mechanism of anti-inflammatory action of simvastatin relates to it could down regulate the expression of AT1R mRNA and up regulate the expression of AT2R mRNA and made the ratios of AT1R mRNA and AT2R mRNA to be normal.