苯妥英钠促进心肌梗死后大鼠心室基质金属蛋白酶活性及胶原沉积  

Phenytoin promotes collagen deposition and activity of matrix metalloproteinases in ventricle in rat after experimental myocardial infarction

作　　者：朱勇[1] 李玉明[1] 周欣[1] 

机构地区：[1]中国人民武装警察部队医学院附属医院心血管病研究所,天津300162

出　　处：《基础医学与临床》2008年第10期1066-1069,共4页Basic and Clinical Medicine

摘　　要：目的研究苯妥英钠对急性心肌梗死(AMI)后大鼠心室基质金属蛋白酶(MMPs)活性和胶原合成的影响及其促进心肌梗死后组织修复的机制。方法用Wistar大鼠建立AMI模型,将大鼠分成苯妥英钠组、对照组和假手术组,在造模后处死动物,取心室,一部分用组织学方法分析;另一部分采用Gelatin Zymography测定MMPs活性。结果苯妥英钠组14 d时梗死区厚度大于对照组,非梗死区心肌横断面积小于对照组;AMI后梗死区胶原容积分数苯妥英钠组高于对照组;AMI后苯妥英钠组Ⅰ/Ⅲ型胶原高于对照组(P<0.05);心室梗死区MMPs活性相对于假手术组明显上调(P<0.05)。结论苯妥英钠可促进AMI后早期梗死区胶原的合成,MMP-2和MMP-9可能参与了此机制。Objective To investigate the mechanisms of phenytoin accelerating healing process. Methods Adult male Wistar rats that survived ligatation of the left coronary artery were randomized to phenytoin group or operation control and compared to sham-operated rats. The time-dependent proteolytic activity of MMP-2 and MMP-9 were detected by gelatin zymography. Picrosirius red staining plus polarized light micrscopy was used for qualitative and quantitative analysis of collagen include collagen volume fraction （CVF） and ratio of type Ⅰ/Ⅲ collagen. In addition, infarct thickness and myocyte cross-sectional area were also evaluated by image analysis. Results Fourteen days after myocardial infartion （MI）, phenytoin reduced infarct wall thinning. Compared with control group, the rats received phenytoin had less myocyte cross-sectional area. Two weeks after MI, CVF in two groups both had significantly dynamic increase and phenytoin accelerated the change. In contrast to control group, ratio of type Ⅰ to type Ⅲ collagen in phenytoin increased more quickly. Apart from these results, phenytoin did little to CVF in non- infarcted region. Analysis of MMPs activity in myocardial extracts by zymography demonstrated that infarction-in- duced expression of proMMPs and active MMPs was both upregulated in phenytoin group and operation control. We found that after MI, MMP-9 activity increased as early as 1 day and reached a maximum then gradually descended, whereas MMP - 2 began to increase rapidly and remain elevated for up to 1 4 days thereafter. Phenytoin seemed to enhance expression of MMP-2 and MMP-9. 1 day after MI, active MMP-9 in phenytoin group expressed an increasing trendency compared to MI control. Conclusion Phenytoin can attenuate the degree of post-infarction left ventricular dilation and expansion of the infarct during the early phase of MI healing. MMP-2 and MMP-9 enhanced by phenytoin probably played a prominent role.

关 键 词：苯妥英钠 心肌梗死 基质金属蛋白酶 胶原 心室重塑 

分 类 号：R542.22[医药卫生—心血管疾病]