川崎病患儿血清MMP-9、TIMP-1、TNF-α水平变化及其与冠状动脉损伤的关系

Changes of serum MMP-9,TIMP-1 and TNF-α levels of patients with Kawasaki disease and its relationship with coronary artery lesions

目的探讨基质金属蛋白酶-9(matix metalloproteinase-9,MMP-9)、金属蛋白酶组织抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在川崎病(Kawasaki disease,KD)患儿血清中的变化及其在冠状动脉损伤中的作用。方法收集2014年10月—2016年1月在本院儿科住院的KD患儿38例,分为冠状动脉损伤(coronary artery lesion,CAL)组16例,无冠脉损伤(non-coronary artery lesion,NCAL)组22例,并以同期住院的普通发热患儿20例、门诊健康体检儿童20例作为对照组。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)测定各组MMP-9、TIMP-1和TNF-α的蛋白水平,应用心脏彩超检查KD患儿CAL情况。计量资料两组比较采用两独立样本t检验和配对t检验,多组间比较采用方差分析,两变量之间相关分析采用Pearson直线相关分析,P<0.05为差异有统计学意义。结果与发热对照组和正常对照组比较,KD急性期血清MMP-9、TIMP-1、MMP-9/TIMP-1、TNF-α的水平显著升高,差异均有统计学意义(F=212.97、185.34、23.68、70.19,均P<0.05);KD缓解期血清MMP-9、TIMP-1、MMP-9/TIMP-1、TNF-α水平与两对照组比较,差异均有统计学意义(F=108.92、87.51、10.81、36.28,均P<0.05),且较急性期显著降低,差异均有统计学意义(t=10.47、19.25、24.63、13.83,均P<0.05)。KD患儿急性期CAL组血清MMP-9、TIMP-1、MMP-9/TIMP-1、TNF-α的水平与NCAL组比较,差异均有统计学意义(t=2.49、5.58、5.99、2.41,均P<0.05)。KD组急性期血清MMP-9水平与TIMP-1和TNF-α水平均呈正相关(r=0.49、0.67,均P<0.05);CAL组急性期血清MMP-9/TIMP-1与左冠状动脉内径(left coronary artery diameter,LCA)/主动脉瓣环内径(aortic ring diameter ratio,AAO)呈正相关(r=0.62,P<0.05),且血清MMP-9与LCA/AAO也有一定的相关性(r=0.55,P<0.05)。结论 MMP-9、TIMP-1、TNF-α共同参与了KD血管炎的病理生理过程,联合检测血清水平可能对早期预测冠状动脉损害有重要价值。

Object ive To investigate the changes of serum matrix metalloproteinase-9（MMP-9）, tissue inhibitor of metalloproteinase-1（TIMP-1）, tumor necrosis factor-α（TNF-α） levels and its potential role of coronary artery lesions of patients with Kawasaki disease（KD）. Methods Thirty-eight inpatient children with KD in department of pediatrics of our hospital from October 2014 to January 2016 were divided into two groups： coronary artery lesion（CAL） group（n=16） and non-coronary artery lesion（NCAL） group（n=22）. Febrile children（n=20） and healthy children（n=20） in the same period were chosen as the control groups. Serum levels of MMP-9, TIMP-1 and TNF-α were measured by enzyme-linked immunosorbent assay（ELISA）. The coronary artery lesions of the children with KD were determined by echocardiography.The comparison of two groups of measuring data with the use of two independent samples t test and paired t test, multiple sets of measurement data comparing with variance analysis, correlation analysis between two groups of variables adopt Pearson linear correlation analysis, P〈0.05 was considered statistically significant. Results Compared with the two control groups, serum MMP-9,TIMP-1,TNF-α levels and MMP-9/TIMP-1 were significantly elevated in the acute phase of KD patients（F=212.97, 185.34,70.19,23.68, all P〈0.05）. In the remission phase, these parameters compared with the two control groups also had statistical significance（F=108.92,87.51,36.28,10.81,all P〈0.05）,and they were decreased significantly compared with the acute phase（t=10.47,19.25,13.83,24.63, all P〈0.05）. In the acute phase, the serum MMP-9,TIMP-1,TNF-α levels and MMP-9/TIMP-1 were significantly in the CAL group higher than in the NCAL groups（t=2.49,5.58,5.99,2.41, all P〈0.05）. The serum MMP-9 level was positively correlated with TIMP-1 and TNF-α levels in the acute phase of KD（r=0.49,0.67, all P〈0.05）. In the CAL group of acute phase, there was positive correlation between MMP-9/TIMP-1 and LCA/AAO（r=0.62, P〈0.05）, serum MMP-9 level and LCA/AAO ratio also had positive correlation（r=0.55, P〈0.05）. Conclusions MMP-9, TIMP-1 and TNF-α are involved in the pathophysiological process of KD vasculitis. Combined detection of them may be of critical value for early prediction of CAL in KD patients.