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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。
Objective To investigate the expression of matix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), tumor necrosis factor-α TNF-α in serum of children with Kawasaki disease (KD) and its role in coronary artery injury. Methods Thirty-eight KD children hospitalized in our pediatric department between October 2014 and January 2016 were randomly divided into coronary artery lesion (CAL) group (n = 16) and non-coronary artery lesion NCAL) group of 22 cases, and in the same period hospitalized children with normal fever in 20 cases, outpatient health examination of 20 children as a control group. The protein levels of MMP-9, TIMP-1 and TNF-α in each group were determined by enzyme-linked immunosorbent assay (ELISA). The CAL of children with KD was detected by echocardiography. Measurement data were compared using two independent samples t-test and paired t-test, between groups were analyzed by analysis of variance, Pearson linear correlation analysis between the two variables, P <0.05 for the difference was statistically significant. Results Compared with the control group and the control group, the levels of serum MMP-9, TIMP-1, MMP-9 / TIMP-1 and TNF-α were significantly increased in the acute phase of KD (F = 212.97 , 185.34,23.68,70.19, all P <0.05). The levels of serum MMP-9, TIMP-1, MMP-9 / TIMP-1 and TNF-α in KD remission group were significantly different from those in the two control groups F = 108.92,87.51,10.81,36.28, all P <0.05), which were significantly lower than those in acute phase (t = 10.47,19.25,24.63,13.83, all P <0.05). The serum levels of MMP-9, TIMP-1, MMP-9 / TIMP-1 and TNF-α in acute KD children with CAL were significantly higher than those in NCAL patients (t = 2.49,5.58,5.99,2.41 , All P <0.05). The levels of serum MMP-9 in acute KD group were positively correlated with the levels of TIMP-1 and TNF-α (r = 0.49,0.67, all P <0.05). The levels of serum MMP-9 / TIMP- There was a positive correlation between left coronary artery diameter (LCA) and aortic ring diameter (AAO) (r = 0.62, P <0.05) and serum MMP-9 and LCA / r = 0.55, P <0.05). Conclusion MMP-9, TIMP-1 and TNF-α are involved in the pathophysiological process of KD vasculitis. Combined detection of serum levels may have important value in the early prediction of coronary artery lesion.