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）表达与心室重构的影响。方法Wistar大鼠正常组18只。阿霉素腹腔注射2．5mg·kg^-1·d^-1，每周3次，累积剂量15mg／kg，分为模型组20只，他汀干预组19只（2周后给予辛伐他汀20mg·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大速率（＋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；而他汀干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，辛伐他汀可进一步上调衰竭心肌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） -1 expression and ventricular remodeling in rats with non-isehemie 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 simvastalin 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 garage. 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 myoeardium, 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%, 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. 011. 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
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2009年第1期70-73,共4页
Chinese Journal of Geriatrics
基金
首都医科大学基础与临床联合课题（2007JL44）
