中期因子对大鼠急性心肌梗死后心室重构和基质金属蛋白酶9水平的影响

目的探讨中期因子(MK)对大鼠急性心肌梗死(AMI)后心室重构及血清基质金属蛋白酶9(MMP-9)水平的影响。方法雄性Wistar大鼠60只采用随机数字抽样法分为4组,每组15只:空白组(Control组),伪手术组(Sham组),AMI组,MK治疗组(MK组)。结扎大鼠左冠状动脉前降支制作AMI模型,模型建立成功后,MK组立即给予MK心肌注射。4周后,取各组剩余大鼠称重,测血流动力学指标;ELISA法测定血清MMP-9水平;心脏称重,计算心体比;取心尖部分切片,一部分MASSON染色,测定左心室游离壁梗死区厚度、长度和梗死面积,心肌梗死区及非梗死区胶原容积分数(CVF),另一部分HE染色,观察毛细血管生成情况。结果 A MI组较Control组和Sham组心室重构和心功能受损明显(P<0.05),血清MMP-9水平明显升高[(6.93±0.09)ng/ml比(4.66±0.06)ng/ml和(4.71±0.06)ng/ml,均为P<0.05];MK组较AMI组心室重构程度轻、心功能改善明显(P<0.05),血清MMP-9水平明显降低[(5.33±0.06)ng/ml比(6.93±0.09)ng/ml,P<0.05 ]。结论 AMI后立即给予MK能够有效抑制心室重构,改善心功能;降低血清MMP-9水平是MK发挥心肌保护作用的途径之一。

Effect of midkine on ventricular remodeling and serum matrix metalloproteinase-9 levels in rats with acute myocardial infarction

Objective To investigate the effect of midkine on ventricular remodeling and serum matrix metalloproteinase-9 （MMP-9） levels in rats with acute myocardial infarction （AMI）. Methods Sixty Wistar rats were divided into four groups using random number sampling method （n = 15 ） ： Control group, sham-operated group （Sham group）, infarct model group （AMI group）, MK treatment group （MK group）. AMI model was established via ligation of left anterior descending coronary artery. Rats in MK group were given injected MK immediately after myocardial infarction. Four weeks later, the rats in each group were weighed and their hemodyuamic parameters were measured; Serum levels of MMP-9 were determined by ELISA method; Then the rats were killed, whole heart was weighed and the heart body weight ratio were calculated. The apexes of hearts were taken, some were performed MASSON staining, thickness and length of infracted free wall, infarct size of left ventricular, infarct area and non-infarcted myocardial collagen volume fraction （CVF） were measured; The others were done HE staining to observe the generation of capillaries. Results Ventricular remodeling and heart dysfunetion in AMI Group were more severe than in Control Group and Sham group （P 〈0. 05） , and serum MMP-9 levels were significantly increased [（6. 93±0. 09） ng/ml vs. （4.66 ± 0. 06） ng/ml and （4. 71 ± 0. 06） ng/ml,both P 〈 0. 05 ]. Ventricular remodeling and heart function in MK group were improved significantly compared with AMI group （P 〈0. 05）, and serum MMP-9 levels were significantly decreased [ （5.33 ±0. 06） ng/ml vs. （6. 93 ±0. 09） ng/ml, P〈0. 05]. Conclusions MK administration shortly after AMI can effectively inhibite ventricular remodeling and improve heart function ; The underlying mechanism of this protective effect may be due to reduced serum MMP-9 levels.