组织激肽释放酶-1对心肌梗死大鼠心肌中巨噬细胞移动抑制因子和基质金属蛋白酶表达的影响

The effect of tissue kallikrein 1on macrophage migration inhibitory factor and matrix metalloproteinases expression in rat with myocardial infarction

目的观察组织激肽释放酶-1(TK-1)对心肌梗死大鼠左心室重塑的影响,探讨该效应与心肌中巨噬细胞移动抑制因子(MIF)和基质金属蛋白酶(MMP)表达的关系。方法结扎雄性Sprague-Dawley(SD)大鼠冠状动脉左前降支构建心肌梗死模型。55只大鼠分为四组:假手术组(n=10)、生理盐水组(n=15)、对照病毒组(n=15)、TK-1组(n=15)。采用心导管法获得大鼠左心室功能相关的血流动力学参数,Masson、苏木素-伊红(HE)染色后观察大鼠心肌梗死面积的大小及炎症细胞浸润,观察心肌中CD34免疫荧光强度以分析梗死心肌中新生血管的分布,Western blot法检测大鼠心肌中TK-1、MIF、MMP-2、MMP-9的表达。结果与假手术组相比,生理盐水组和对照病毒组大鼠心功能相关的血流动力学参数明显恶化,左心室梗死面积增大,炎症细胞明显浸润,梗死心肌中的新生血管密度较低,MIF、MMP-2、MMP-9的表达增加(P<0.05);与对照病毒组相比,TK-1组的大鼠心功能相关的血流动力学参数明显改善[左心室收缩压:假手术组(134.82±10.33)比生理盐水组(79.67±4.77)比对照病毒组(81.34±5.78)比TK-1组(102.65±7.34)mm Hg,F=94.00,P<0.05],左心室梗死面积减少,炎症细胞浸润减少,梗死心肌中的新生血管密度增加,MIF、MMP-2、MMP-9表达下降(P<0.05)。结论TK-1可部分逆转心肌梗死大鼠的左心室重塑,这种效应可能与心肌中MIF、MMP-2、MMP-9的表达下调有关。

Objective To investigate the effect of tissue kallikrein 1(TK-1)on cardiac remodeling in myocardial infarction(MI)rats,and to explore the relationship between this effect and myocardial expression of macrophage migration inhibitory factor(MIF)and matrix metalloproteinases(MMP).Methods The rat model of MI was constructed by ligating left anterior descending arteries of Sprague-Dawley(SD)rats.Fifty five SD rats were divided into four groups:sham operation group(n=10),saline group(n=15),control virus group(n=15)and TK-1group(n=15).In addition,the hemodynamic parameters related to cardiac function were obtained by cardiac catheterization.Infarct area and infiltration of inflammatory cells were determined by Masson stainning and hematoxylin and eosin(HE)stainning,respectively.Angiogenesis was detected by CD34immunofluorescence intensity.Transfection with recombinant adenovirus and TK-1expression in myocardium of rats were verified by immunofluorescence and Western blot.MIF,MMP-2and MMP-9expression was determined by Western blot.Results Compared with sham operation group,rats in the saline and control virus groups showed significantly deteriorated hemodynamic parameters related to cardiac function,increased infarct area,and infiltration of inflammatory cells,decreased angiogenesis in the infarcted myocardium,and increased expression of MIF,MMP-2,and MMP-9(P<0.05).However,compared with the control virus group,rats in the TK-1group had significantly improved hemodynamic parameters related to cardiac function[left ventricular systolic blood pressure:sham operation group(134.82±10.33)vs saline group(79.67±4.77)vs control virus group(81.34±5.78)vs TK-1group(102.65±7.34)mm Hg,F=94.00,P<0.05],markedly reduced infarct area,less inflammatory cell infiltration and elevated angiogenesis.The expressions of MIF,MMP-2,and MMP-9decreased(P<0.05).Conclusions TK-1can partially reverse cardiac remodeling in MI rats,and this effect may be related to down-regulation of MIF,MMP-2,and MMP-9expression in the myocardium.