Effects of simvastatin on heme oxygenase-1 expression and ventricular remodeling in rats with non -ischemic heart failure / 中华老年医学杂志

ABSTRACT

Objective To investigate the effect of simvastatin on heme oxygenase (HO) -1expression and ventricular remodeling in rats with non-ischemic heart failure. Methods Seventy eight male Wistar rats were randomized into three groups normal control group (n = 18), model group and simvastatin group (n= 60). Male Wistar rats in model and simvastatin group were given adrimycin(ADR) in an accumulated dose of 15 mg/kg for two weeks (2.5 mg /kg, peritoneal injection, three times per week), and 8 rats were dead. The survival rats (n= 52) were then randomly divided into two groups model group (n=26) and simvastatin group (n=26), and 6 rats were dead in model group, while 7 dead in simvastatin group at the end of the study. Then rats in simvastatin treatment group(n=19)were given simvastatin 20 mg·kg-1·d-1 by gavage for four weeks,and rats in model group (n=20) and in control group (n=18) were treated with 5% glucose by gavage.At the forth week, another 9 rats were selected into the study and given ADR with an accumulated dose of 15 mg/kg for two weeks. The hemodynamics, mRNA expression of HO-1 in myocardium, left ventricular function as well as hydroxyproline were measured at the end of the sixth week. Results At the sixth week, compared with control group, systolic (+) and diastolic (-) function of the left ventricule (±LVdp/dtmax) of rats in model group and simvastatin group were reduced significantly, and the reduction amplitudes of + LVdp/dtmax and -LVdp/dtmax were 28.2%, 11.9% and 33.0%,27.9%,4, respectively (F = 4.899,3. 890, all P<0.01). The + LVdp/dtmax of rats in simvastatin group was higher than that in model group (F= 2.461, P<0.05). The content of myocardium hydroxyproline was elevated from the end of the second week [(485.0±52.9)g/kg vs. (364.0±41.6)g/kg,F=0.441 ,P<0.01]. At the end of the sixth week, the content of myocardium hydroxyproline of model group elevated continuously [(572.9±75.4) g/kg vs. (485.0±52.9)g/kg, F=0.654,P<0.05], but not for simvastatin group [(475.9±86.5) g/kg vs. (485.0±52.9)g/kg, P>0.05]. The mRNA expression of HO-1 in myocardium 'in model group was higher than that in control group [(0.6217±0.1229) vs. (0.2475±0.1053), F = 0.128, P < 0.01]. The mRNA expression of myocardium HO-1 was increased further by simvastatin treatment [(0.7860±0.1133) vs. (0.6217±0.1229),F=3.622,P<0.05]. Conclusions Compared with control group, the myocardial HO-1expression of heart failure rats is increased. Simvastatin treatment enhances the myocardium HO-1 expression further and alleviates myocardial injury and the degree of heart failure.