摘要
目的:探讨重组人促红细胞生成素(rhEPO)对心肌梗死大鼠间质和基质金属蛋白酶(MMP-2,MMP-9)蛋白及mRNA的影响。方法:将48只SD大鼠随机分为心肌梗死(MI)组、MI药物(MIE)组、假手术(SH)组、假手术药物(SHE)组。结扎前降支建立梗死模型。4周处死大鼠,测量其梗死面积、胶原容积分数、超声心动图,免疫组化及RT-PCR法测定MMP-2、MMP-9蛋白及mRNA在大鼠心室肌中的表达、转录情况。结果:4周时,左室梗死面积MIE组较MI组明显减少(P<0.01);梗死交界区MI组胶原容积分数较MIE组升高(P<0.01);超声心动图显示MI组和MIE组左室舒张末期内径(LVDd)、左室收缩末期内径(LVDs)、左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)测值均高于SH和SHE组,左室射血分数(LVEF)和左室短轴缩短率(LVFS)测值均低于SH组和SHE组(P<0.01),MI组LVDd、LVDs、LVEDV、LVESV测值高于MIE组,LVEF和左室短轴缩短率测值低于MIE组(P<0.05);MI、MIE组MMP-2、MMP-9蛋白及mRNA表达较SH、SHE组增高(P<0.01),MIE组MMP-2、MMP-9表达较MI组降低(P<0.01)。结论:经rhEPO早期干预后,大鼠心功能明显改善,可能通过抑制MMPs蛋白和mRNA的表达、降低胶原含量、减少梗死面积、抑制间质纤维化共同改善心肌间质重塑。
Objective:The purpose of this study was to examine the effects of EPO on matrix metalloproteinase and extraeellular matrix remodeling after myocardial infarction. Method: Fourty eight male Sprague Dawley rats were randomly divided into four groups:SH group not treated with rhEPO,SHE treated with rhEPO, MI not trea- ted with rhEPO, MIE treated with rhEPO. The MI and MIE group were established by ligation of left anterior descenidng artery. At four weeks, infarct size, collagen volume fraction, echocardiography, and matrix metalloproteinase-2, 9 (MMP 2, MMP-9) were measured by RT-PCR and immunohistochemistry. Result: Four weeks after myocardial infraction the expression of MMP-2, MMP-9 protein and mRNA in MI and MIE group were significantly higher compared to SH group and SHE group (P〈0.01), while the expression of MMP-2, MMP-9 in MIE group were lower than MI group(P〈0.01). Four weeks after myocardial infraction the infarct size, collagen volume fraction in MIE group were significantly lower compared to MI group(P〈0.01). Echocardiography reveled that four weeks following myocardial infraction, the LVDd, LVDs, LVEDV, LVESV in MI group were enlarged, and LVEF and LVFS were decreased compared to SH and SHE group(P〈0.01). Conclusion: RhEPO significantly attenuated myocardial extracellular matrix remodeling and improved LV function, which was associated with inhibition of the expression of MMP 2.MMP-9.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2009年第1期52-55,共4页
Journal of Clinical Cardiology
关键词
促红细胞生成素
心肌梗死
间质重塑
基质金属蛋白酶
erythropoietin
myocardial infarction
extracellular matrix remodeling
matrix metalloproteinase