巨噬细胞游走抑制因子及其下游信号通路血浆水平与冠状动脉病变程度的相关性

Association between plasma macrophage migration inhibitory factor concentration and coronary artery lesion severity

目的通过测定不同类型冠心病患者血浆中巨噬细胞游走抑制因子（MIF）及其下游信号通路激活蛋白-1（AP-1）和基质金属蛋白酶-9（MMP-9）水平，探讨MIF、AP-1和MMP-9信号通路与冠状动脉病变的关系。方法根据选择性冠状动脉造影结果将142例入院患者分为冠心病组和对照组。冠心病组根据临床诊断分为稳定型心绞痛（SAP）组和急性冠状动脉综合征（ACS）组；根据冠状动脉病变类型分为A型病变、B型病变和C型病变组；并根据造影结果对冠状动脉病变进行Gensini评分；采用ELISA方法测定血浆MIF、AP-1、MMP-9浓度水平。分析各组间MIF、AP-1、MMP-9浓度水平的差异，及其与冠状动脉病变严重程度间的相关性。结果冠心病组的甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）明显高于对照组（P〈0．05），高密度脂蛋白胆固醇（HDL-C）明显低于对照组（P〈0．05）；冠心病组MIF[（14．97±2．11）μg/L]及其下游信号通路AP-1（1．43±0．33）和MMP-9[（1．48±0．14）μg／L]水平明显高于对照组[MIF：（9．07±1．28）μg／L；AP-1：0．71±0．13；MMP-9：（1．01±0．07）μg／L，均P〈0．05]，ACS组MIF[（16．66±2．56）μg／L]、AP-1（1．56±0．22）和MMP-9[（1．58±0．14）μg／L]水平明显高于SAP组[MIF：（11．01±2．12）μg／L，AP-1：1．04±0．25，MMP-9：（1．25±0．07）μg／L，均P〈0．05]。随着冠状动脉病变类型和冠状动脉病变程度的加重，MIF、AP-1和MMP-9浓度逐渐升高（P〈0．05）。逐步回归分析示HDL—C与Gensini评分呈负相关，LDL-C、MIF、MMP-9、活性AP-1数量与之呈正相关。AP-1与MMP-9水平呈显著正相关（P〈0．05）。结论MIF及其下游信号通路AP-1和MMP-9血浆水平与冠状动脉病变的严重性呈明显正相关，其对易损斑块的形成有促进作用，并对冠状动脉病变情况及斑块稳定性有一定的预测价值。

Objective To investigate the relationship between the plasma macrophage migration inhibitory factor（ MIF）, activator protein-1 （AP-1） and MMP-9 concentrations and the severity of coronary artery lesions in coronary heart disease （CHD） patients. Methods Patients were divided into normal controls （ n = 35 ）, stable angina pectoris （ SAP, n = 32） and acute coronary syndrome （ ACS, n = 75 ） according to the coronary angiography （CAG）, clinical and laboratory examinations. The CAG severity and extent of coronary lesions were analyzed by means of Gensini coronary score system. Enzyme linked immunosorent assay was used to measure the plasma MIF, AP-1 and MMP-9 concentrations. Results Plasma MIF, AP-1 and MMP-9 concentrations were significant increased in CHD patients [ MIF： （ 14. 97 ± 2. 11 ） μg/L, AP-1 ： 1.43 ± 0. 33, MMP-9 ： （ 1.48 ± 0. 14） μg/L ] compared to those in control group [ MIF： （9.07±1.28） μg/L,AP-1：0. 71 ±0. 13, MMP-9：（1.01 ±0.07） μg/L, all P〈0.05]. The MIF, AP-1 and MMP-9 concentrations in ACS group [ MIF ： （ 16. 66 ± 2. 56） μg/L, AP-1 ： 1.56 ±0.22, MMP-9 ： （ 1.58 ±0. 14） μg/L] were also significant higher than those in SAP group[MIF： （11.01 ±2. 12） μg/L, AP-1 ： 1.04 ± 0. 25, MMP-9 ： （ 1.25±0. 07 ） μg/L, all P 〈 0. 05 ] and there was significant positive correlation between MIF, AP-1 and MMP-9 concentrations and the Gensini score of coronary artery lesions （ all P 〈 0. 05）. AP-1 was positively correlated with MMP-9 in CHD patients （ P 〈 0. 05）. Conclusions Plasma MIF, AP-1 and MMP-9 concentrations were positively correlated to the severity of coronary lesions in CHD patients. Higher MIF, AP-1 and MMP-9 concentrations in ACS patients than in SAP patients might suggest higher plaque instability in ACS patients.