辛伐他汀对非缺血性心力衰竭大鼠血红素氧合酶-1表达和心室重构的影响

摘要

目的 观察辛伐他汀对盐酸多柔比星(商品名:阿霉素)制备的非缺血性心力衰竭模型大鼠血红素氧合酶-1(HO-1)表达与心窒重构的影响. 方法 Wistar大鼠正常组18只.阿霉素腹腔注射2.5 mg·kg-1·d-1,每周3次,累积剂量15 mg/kg,分为模型组20只,他汀干预组19只(2周后给予辛伐他汀20 mg·kg-1·d-1灌胃,共4周).另选9只大鼠,于上述大鼠干预3周购进,经1周适应环境后,给予上述方法阿霉素腹腔注射,为2周组.分别进行血流动力学检查,测定心肌HO-1的mRNA表达、羟脯氨酸含量与病理分析. 结果 6周时模型组与他汀干预组的左心室收缩最人速率(+LVdp/dtmax)与舒张的最大速率(-LVdp/dtmax)均明显下降,其中+LVdp/dtmax两组分别下降28.2%与11.9%,-LVdp/dtmax两组分别下降33.0%与27.9%(F分别为4.899、3.80均为P<0.01);他汀干预组的±LVdp/dtmax较模型组分别高22.6%和7.5%,差异有统计学意义(F=2.461,P<0.05).2周时大鼠心肌羟脯氨酸含量即开始升高,分别为[(485.0±52.9)g/kg和(364.0±41.6)g/kg,F=0.441,P<0.01];6周时,模型组心肌羟脯氨酸含量继续升高为(572.9±75.4)g/kg,F=0.654,P<0.05;而他汀下预组心肌羟脯氨酸含量与2周组[(475.9±86.5)g/kg]比较,差异无统计学意义.6周时模型组大鼠心肌HO-1表达较正常组增高,分别为0.6217±0.1229与0.2475±0.1053,F=0.128,P<0.01;辛伐他汀干预使HO-1的表达进一步升高,分别为0.7860±0.1133和0.6217±0.1229,F=3.622,P<0.05. 结论心力衰竭大鼠心肌HO-1表达增高,辛伐他汀可进一步卜调衰竭心肌HO-1的表达,从而减轻心肌损伤与心力衰竭的程度.%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.