卡托普利逆转阿霉素心肌病大鼠左室重构机制的研究  

The angiotensin-converting enzyme inhibitor captopril attenuates left ventricular remodeling and failure in a rat model of adriamycin-induced dilated cardiomyopathy

作　　者：戚本玲[1] 刘洪智[1] 曹林生[1] 成蓓[1] 管思明[1] 刘承云[1] 张湖萍[1] 何平[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院老年病科,武汉市430022

出　　处：《中华老年医学杂志》2006年第9期691-695,共5页Chinese Journal of Geriatrics

摘　　要：目的探讨血管紧张素转换酶抑制剂卡托普利逆转阿霉素心肌病大鼠左室重构和改善心功能的作用机制。方法雄性Wistar大鼠分3组:(1)阿霉素心肌病组(ADR-DCM组,25只):阿霉素2．5 mg／kg,尾静脉注射,每周1次,连续10周;(2)ADR-DCM+卡托普利治疗组(ACEI组,25只):卡托普利50 mg·kg-1·d-1灌胃治疗;(3)健康对照组(对照组,10只)。阿霉素注射2周后行超声和血流动力学检测,硫代巴比妥酸法检测丙二醛(MDA)含量,苦味酸天狼星红染色进行左室胶原特异染色及定量分析,计算胶原容积分数(CVF),RT-PCR检测金属基质蛋白酶(MMP)-2、MMP-9及金属蛋白酶组织抑制因子(TIMP)-1的表达,明胶酶谱法检测MMPs活性。结果ACEI组较ADR-DCM组病死率明显降低(12％和40％,P<0．01)。与对照组比较,ADR-DCM组大鼠左室内径扩大及心功能明显下降,ACEI组左室内径增加程度降低及心功能各项指标改善。ADR-DCM组MDA含量较对照组增加(P<0．01),而ACEI治疗可降低MDA含量。苦味酸天狼星红染色显示ADR-DCM组左室胶原明显增加,CVF增高;ACEI组CVF显著降低(P<0．01)。ADR-DCM组左室心肌MMP-2、MMP-9mRNA表达较对照组明显升高(P<0．01),MMPs明胶酶活性显著增加(P< 0．01),ACEI明显抑制MMP-2、MMP-9mRNA表达,降低升高的MMPs明胶酶活性,而TIMP-1的表达在3组差异无统计学意义(P>0．05)。结论阿霉素心肌病大鼠左室心肌MMPs表达及活性上调,卡托普利部分通过抑制MMPs表达及活性逆转阿霉素心肌病大鼠左室重构,改善心功能。Objective To determine whether and how angiotensin-converting enzyme inhibitor （ACEI） captopril attenuates left ventricular （LV） remodeling and failure in a rat model of adriamycin -induced dilated cardiomyopathy（ADR-DCM）. Methods Weight-matched adult male Wistar rats were randomly divided into 3 groups： （1）The adriamycin group（ADR, n= 25）, who received 2.5 mg·kg^-1 of ADR injected via a tail vein once a week for 10 weeks; （2）Concomitant captopril and ADR group （ACEI,n=25）, who were administered captopril by gavage at a dose of 50 mg·kg^-1·day^-1 （3）The control group （n= 10）. Hemodynamics and echocardiographic measurements were carried out after 12 weeks of ADR treatment. Finally, LV samples were collected at the 12th week, the content of malondialdehyde （MDA） in LV was investigated by the methods of TBA, the expression and distribution of collagen in LV were investigated with picric acid-sirius red staining techniques. Semi-quantitative analysis was used to evaluate the collagen volume fraction （CVF）. The mRNA expressions of metalloproteinase-2 （MMP 2）, MMP-9, TIMP-1 were measured by RT-PCR. The MMP-2 and MMP-9 gelatinolytic activities were measured by gelatin zymography. Results The mortality was significantly lower in ACEI group than in ADR group （12% vs 40%, P〈0. 01）. LV cavity dilatation was significantly attenuated in ACEI group. Captopril partially normalized LV contractile function which was significantly decreased in ADR rat. The level of MDA was higher in the ADR group than in the control group （P〈0.01）, and was significantly reduced in ACEI group. Myocardial collagen content in LV increased and myocardial fibrosis occurred, LV CVF increased significantly in ADR group, but LV CVF was partly reversed by captopril treatment （P 〈 0. 0 1 ） . The mRNA expressions of LV MMP 2 , MMP 9 were increased in ADR rat and attenuated by captopril treatment （all P〈0.01）, but there was no change in TIMP-1 mRNA expression （P〉0.05） LV myoca

关 键 词：基质金属蛋白酶类 阿霉素 心肌疾病 血管紧张素转换酶抑制药 

分 类 号：R542.21[医药卫生—心血管疾病]