普罗布考对心衰大鼠心肌MMP-3、TIMP-3及OPN表达的影响  

Effect of probucol on expressions of MMP-3、TIMP-3,OPN in myocardium of rat with heart failure

作　　者：张冰 马金国 吴刚 赵继义[2] 黄明学[2] 周立君[2] 

机构地区：[1]内蒙古呼伦贝尔市人民医院心血管内科,内蒙古呼伦贝尔021008 [2]哈尔滨医科大学附属第一医院心血管内科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2015年第2期115-120,共6页Journal of Harbin Medical University

摘　　要：目的检测普罗布考(probucol,PRO)对心衰大鼠心肌中基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶抑制剂-3(TIMP-3)及骨桥蛋白(osteopontin,OPN)表达的影响,探讨PRO对心衰的干预作用。方法采用阿霉素(adriamycin)诱导大鼠心衰模型,120只雄性Wistar大鼠,15只为对照组,105只诱导心衰后分成2组:普罗布考治疗组(PRO组)、心衰组(ADR组)。将PRO组给予普罗布考500 mg·kg-1·d-1蒸馏水配液灌胃,对照组、ADR组给予同等剂量蒸馏水灌胃,连续干预4周。行心脏超声、心肌组织病理及超微结构检测,免疫组化法测OPN、MMP-3、TIMP-3。结果 1心衰组较对照组左室射血分数(EF)、左室短轴缩短率(FS)均减低(P<0.01),鼠体重、全心重/体重、左室重量变化显著(P<0.05,P<0.05,P<0.01);OPN、MMP-3表达升高,TIMP-3降低,差异具有统计学意义(P<0.05)。2PRO组较ADR组大鼠EF、FS明显提高(分别P<0.05,P<0.01),MMP-3、OPN表达降低,TIMP-3表达升高,差异均有统计学意义(P<0.05)。3PRO组与对照组均无显著差异。结论普罗布考可降低大鼠心衰时心肌细胞外基质OPN和MMP-3的合成,促进TIMP-3的表达,有逆转心肌重构,改善心功能作用。Objective To detect the influence of probucol （ PRO） on the expressions of matrix metalloproteinases-3 （ MMP-3 ） , matrix metalloproteinases inhibitor-3 （ TIMP-3 ） , and os-teopontin （ OPN） in myocardium of rat with heart failure and the interventional effect of PRO on cardiac failure .Methods Rat model of heart failure was induced by adriamycin among 120 male Wistar rats , 15 rats for control group , and 105 rats were divided into 2 groups after in-duced heart failure：probucol group （ PRO） and heart failure group （ ADR） .PRO group were received probucol 500 mg · kg -1 · d-1 and distilled water with liquid gavage , while control group and ADR group were given the same dose of distilled water , with continuous intervention for 4 weeks .Echocardiography , myocardial histopathology and ultrastructure detection were＆nbsp;performed, OPN, MMP-3, TIMP-3 were detected by immunohistochemical method .Results①In ADR group, left ventricular ejection fraction （EF）, left ventricular fractional shortening （ FS） were lower compared with control group （ P〈0.01 ） , the weight of the rat , whole heart heavy weight/body weight , left ventricular weight changed significantly （ P〈0.05 , P〈0.05 , P〈0.01 ）;OPN, MMP-3 expression was increased , TIMP-3 was lower , the differences were statistically significant （P〈0.05）.②In PRO group, EF, FS increased significantly compared with ADR group （ P〈0.05 , P〈0.01 ） , MMP-3 , OPN expression was decreased , TIMP-3 ex-pression was increased , the differences were statistically significant （ P〈0.05 ）;③There was no significant difference between PRO group and control group .Conclusion Probucol can re-duce synthesis of myocardial extracellular matrix OPN , MMP-3 and elevated TIMP-3 , and re-versing myocardial remodeling and improving cardiac function .

关 键 词：心力衰竭 普罗布考 MMP-3 TIMP-3 骨桥蛋白 

分 类 号：R541.6[医药卫生—心血管疾病]