苯妥英钠对大鼠急性心肌梗死后心室重塑的影响  

Effects of Phenytoin on ventricular remodeling in rats 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：《山东医药》2008年第2期8-11,共4页Shandong Medical Journal

摘　　要：目的探讨苯妥英钠促进心肌梗死后组织修复的机制。方法将175只Wistar大鼠随机分为苯妥英钠组、对照组和假手术组三组。苯妥英钠组及对照组开胸结扎冠状动脉,建立AMI模型。造模后苯妥英钠组腹腔注射苯妥英钠100 mg/(kg.d),对照组腹腔注射等量的生理盐水;假手术组开胸后不结扎冠状动脉,亦不用药。分别于造模后第1、3、7、14 d时各处死动物61只,取心室分为两部分,一部分用组织学方法分析Ⅰ/Ⅲ型胶原比值、心肌横断面积、胶原容积分数和梗死区厚度;另一部分分割为梗死区和非梗死区,采用Gelatin Zymography测定梗死区基质金属蛋白酶(MMP)-2和MMP-9活性。结果苯妥英钠组14 d时梗死区厚度大于对照组(P<0.01),非梗死区心肌横断面积14 d时小于对照组(P<0.01);梗死区胶原容积分数整体呈上升趋势,在同一时间点高于对照组,14 d时变化尤为明显(P<0.01)。梗死区MMPs活性明显高于假手术组,其中MMP-9活性在1 d后迅速升至最高峰,此后逐渐下降,14 d时尚未回至正常水平,而MMP-2活性则持续升高,14 d时最高,并有继续上升趋势。对照组整体变化趋势与苯妥英钠组相同,但后者MMPs活性增强更为明显,1 d时活化型MMP-9已表现出这一特点。结论苯妥英钠可促进AMI后早期梗死区胶原合成,有效减缓早期梗死区的膨展;MMP-2和MMP-9活性在AMI后呈现动态升高趋势;苯妥英钠通过加强这一变化、促进炎症反应的进程,从而加速梗死区的自身修复。Objective To investigate the possible mechanisms that phenytoin accelerates the healing process in myocardial infarction rats. Methods 175 adult male Wistar rats that survived ligatation of the left coronary artery were randomized into phenytoin grouμoperation control group and sham-operation group. Coronary arteries were ligated in phenytoin group and control group to establish AMI model. Rats in phenytoin group were injected phenytoin （ 100 mg·kg^-1·day^-1 ） intraperitoneally, and those in control group were injected with the same volume salt. Rats in sham-operation group were just opened chest. The rats were sacrificed at the first, third, seventh, fourteenth day respectively. The time-dependent proteolytic activity of MMP-2 and MMP-9 were detected by gelatin zymography serially. 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 myecyte cross-sectional area were also evaluated by image analysis. Results 14 days after myocardial infartion （ MI）, , the infracted ventricular free wall in phenytoln group（4.00 mm±0. 84 mm） was thicker than that in control group（3.16 mm±0.55mm） ,P 〈 0. 01, whereas the rats in phenytoin group had less myecyte cross-sectional area compared with the control group（ 372. 12μm^2± 70.55 μm^2 versus 416.95 μm^2±61.54 μm^2, P〈0.01）. 2 weeks after MI, CVF in two groups both had significantly dynamic increase and phenytoin could accelerate the beneficial change （76.81% ± 8.32% versus 84.46% ± 4.26%, P 〈 0.01 ）. In contrast to control grouμ ratio of type I to type Ⅲ collagen in phenytoin group increased more quickly. 14 days after MI, phenytoin group achieved 36.88 ± 18.60, whereas operation control group is only 22.05 ± 7.43（ P 〈0.05）. Apart from these results, phenytoin did little to CVF in non-infarcted region. Analysis of MMPs activity in myocardial extracts

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：R542.2[医药卫生—心血管疾病]