摘要
目的探讨心力衰竭（心衰）时心脏基质金属蛋白酶2（MMP-2）、9（MMP-9）及其组织抑制因子1（TIMP-1）、2（TIMP-2）基因表达及其与心肌纤维化的关系。方法用降主动脉缩窄术建立心衰模型。sD大鼠随机分成6组。分别在氯沙坦5mg／kg、辛伐他汀2mg／kg以及两药合用（联合投药组）投药后1、3、5周动态测定左室舒张末期内径、左室收缩末期内径及左室后壁厚度、左室短轴缩短率。ELISA法检测B型利钠肽浓度。Masson染色观察心肌胶原情况。RT—PCR法检测心室MMP-2、MMP-9和TIMP-1、TIMP-2基因表达。结果投药后5周各组胶原容积分数比较差异有统计学意义（P〈0．01），投药各组较降主动脉缩窄（模型）组下降（P〈0．05），尤其联合投药组下降更明显（P〈0．01）。MMP-2 mRNA和MMP-9 mRNA在投药各组与模型组差异无统计学意义（P〉0．05）；但TIMP-1 mRNA和TIMP-2 mRNA在投药各组明显低于模型组（P〈0．01），联合投药组降低更明显（P〈0．05）。结论心衰模型大鼠MMP-2 mRNA、MMP-9 mRNA和TIMP-1 mRNA、TIMP-2 mRNA表达升高可能是压力负荷大鼠心肌胶原含量增加的分子机制之一，氯沙坦、辛伐他汀以及联合投药均能下调TIMP-1 mRNA、TIMP-2 mRNA水平，缓解心肌重构，尤其联合投药组效果更明显。
Objective To investigate the effects of simvastatin（Sim） and losartan（Los） on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts. Methods The pressure overload model was induced by descending aortic constriction （DAC） in rats. SD rats were randomized into 6 groups （ n = 20 each） ： normol control group, control sham group, DAC group, Los group （DAC ＋Los, 5 mg/kg）, Sire group （DAC ＋Sire, 2 mg/kg）, Los＋Sim group （DAC ＋ Los ＋ Sim, Los 5 mg/kg, Sim 2 mg/kg）. Water, Los or Sim drug was administrated by garage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR. Results Collagen volume fraction （CVF） in DAC group was significantly higher than the normal control and sham groups （ P 〈 0. 01 ） which could be significantly reduced by Los and Sim （P 〈 0. 05 ）, especially in DAC ＋ Los ＋ Sim group （ P 〈 0. 01 ）. The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups （P 〈0. 01 ）. Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions （P 〈 0. 01 ） while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged （ P 〉 0. 05 ）. Conclusion Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2009年第10期887-891,共5页
Chinese Journal of Cardiology
关键词
心力衰竭
充血性
基质金属蛋白酶
心肌
纤维化
干预性研究
Heart failure, congestive
Matrix metalloproteinases
Myocardium
Fibrosis
Intervention studies
