Effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in immature rabbits with chronic heart failure

Abstract

Objective To observe the effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in immature rabbits with chronic heart failure. Methods Thirty-six male New Zealand big-eared immature rabbits were randomly divided into 3 groups: Adriamycin(ADR)+ Simvastatin group(ADR-s group, n=12), in which ADR(1.5 mg/kg) received injection via the auricular vein of rabbits weekly, and the rabbits received oral Sim-vastatin [1.5 mg/(kg·d)] simultaneously for 12 weeks; ADR group(n=12), in which the rabbits received ADR like ADR-S group, and 9 g/L saline instead of Simvastatin; control group (CON group, n=12), which received the same amount of 9 g/L saline.Echocardiography examination was performed in 13th week.Myocardial fibrosis degree was detected by using MASSON staining, and the myocardial apoptosis was detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling.Colorimetric method was used to detect the myocardial concentration superoxide dismutase (SOD) and malondialdehyde (MDA). Enzyme-linked immunosorbent assay was used to detect serum B-type brain natriuretic peptide (BNP) level. Results (1) In CON group, the immature rabbits were all alive.Four rabbits died in ADR group, and the survival rate was 66.7%, while 2 rabbits died in ADR-s group, and the survival rate was 83.3%.(2)Compared with CON group, the left ventricular end diastolic diameter (LVEDd) and left ventricular end systolic diameter (LVESd) in ADR-s group and ADR group increased [(11.90±1.09) mm, (11.34±0.92) mm vs.(10.73±0.48) mm; (9.80±0.88) mm, (8.47±1.23) mm vs.(7.31±0.36) mm]; left ventricular fractional shortening(LVFS) and left ventricular ejection fraction(LVEF) decreased [(17.65±1.70)%, (22.58±2.19)% vs.(31.79±2.58)%; (41.35±3.19)%, (49.17±3.53)% vs.(64.34±3.97)%], and all the differences were significant(all P<0.05); LVEDd and LVESd in ADR-s group were lower than those of ADR group, while LVEF and LVFS in ADR-s group were higher than those of ADR group, and the differences were significant(all P<0.05). (3) MASSON staining: compared with ADR group, there was less myocardial cell hyperplasia of fibrous tissue in ADR-s group.(4)Compared with CON group, the apoptosis index was higher in ADR and ADR-s group[(34.25±11.13)%, (24.00±6.85)% vs.(16.58±5.34)%], but ADR-s group had less than ADR group, and the diffe-rences were significant (all P<0.05). (5) Compared with ADR group, SOD activity of ADR-s group was higher[(13.40±2.68) kU/L vs.(10.66±2.99) kU/L], but MDA content was lower[(5.67±1.36) μmol/mg vs.(7.08±0.98) μmol/mg], and the differences were significant (all P<0.05). (6) Serum BNP level in ADR group and ADR-s group was higher than that of the CON group[(33.28±9.58) μg/L, (26.71±6.72) μg/L vs.(13.56±2.82) μg/L], while was higher in ADR group than that of ADR-s group, and the differences were significant (all P<0.05). Conclusions Simvastatin can protect cardiac function of immature rabbits with chronic heart failure.The possible mechanism may be the up-regulation of myocardial SOD activity, reduction of cell lipid peroxidation and inhibition of myocardial apoptosis. Key words: Simvastatin; Adriamycin; Chronic heart failure; Myocardial apoptosis; Oxidative stress