血清和肽素及基质金属蛋白酶9在儿童慢性心力衰竭中的变化及意义

摘要

目的 探讨血清和肽素(Copeptin)、基质金属蛋白酶-9(MMP-9)在儿童慢性心力衰竭(CHF)中的变化及其临床意义.方法 选取186例CHF患儿为CHF组,其中心功能Ⅱ级78例、Ⅲ级65例、Ⅳ级43例;扩张型心肌病57例、先天性心脏病68例、其他疾病61例;并设85例健康体检儿童为对照组.采用酶联免疫吸附法测定血清Copeptin及MMP-9水平,双向侧流免疫法测定氨基末端脑钠肽前体(NT-proBNP)水平;超声心动图测定左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS).应用ROC曲线分析血清Copeptin及MMP-9对CHF的诊断价值,Pearson相关分析血清Copeptin及MMP-9与各心功能指标相关性.结果 不同心功能组(Ⅱ、Ⅲ、Ⅳ级)的血清Copeptin、MMP-9及NT-proBNP水平均高于对照组,且随心功能损害加重而逐渐升高,差异有统计学意义(P均<0.05).与对照组和心功能Ⅱ级组比较,心功能Ⅲ级、Ⅳ级组LVESD、LVEDD均升高,而LVEF、LVFS均降低;与心功能Ⅲ级组比较,心功能Ⅳ级组LVESD、LVEDD均升高,而LVEF、LVFS均降低,差异有统计学意义(P<0.05).ROC曲线显示,血清Copeptin、MMP-9、NT-proBNP及三项联合诊断CHF的曲线下面积(AUC)及95％CI分别为0.845(0.781～0.914)、0.806(0.736～0.883)、0.894(0.828～0.962)、0.925(0.846～0.983),其最佳阈值分别为12.5 pmol/L、175.3μg/L、2037.0 ng/L.血清Copeptin水平与MMP-9呈显著正相关(r=0.807,P<0.001).结论 血清Copeptin及MMP-9可能参与CHF患儿心室重塑,有望作为诊断CHF和心功能判断的良好指标.%Objective To investigate the changes of serum Copeptin and matrix metalloproteinase-9 (MMP-9) in children with chronic heart failure (CHF) and its clinical significance. Methods A total of 186 children with CHF were selected for CHF group, including 78 cases of cardiac function grade Ⅱ, 65 cases of grade Ⅲ, and 43 cases of grade Ⅳ. There were 57 cases of dilated cardiomyopathy, 68 cases of congenital heart disease and 61 cases of other diseases. Another 85 healthy children from health checkup were chosen as controls. The levels of serum Copeptin and MMP-9 were determined by enzyme linked immunosorbent assay (ELISA), and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by bidirectional lateral flow immunoassay. The left ventricular end diastolic dimension (LVEDD), left ventricular end systolic dimension (LVESD), left ventricular ejection fraction (LVEF), and left ventricular short fraction shortening (LVFS) were measured by echocardiography. ROC curve was used to analyze the diagnostic value of serum Copeptin and MMP-9 in CHF. The correlation of serum Copeptin and MMP-9 with the cardiac function indices were examined by Pearson correlation analysis. Results The levels of serum copeptin, MMP-9, and NT-proBNP in different cardiac function groups (Ⅱ, Ⅲ, Ⅳ) increased gradually with the aggravation of the cardiac function damage and were higher than those in control group, and the differences were statistically significant (P<0.05). Compared with the control group and cardiac function grade Ⅱ group, the levels of LVESD and LVEDD were increased and the levels of LVEF and LVFS were decreased in the grade Ⅲ and Ⅳ groups. Compared with the grade Ⅲ group, the levels of LVESD and LVEDD were increased and the levels of LVEF and LVFS were decreased in the grade Ⅳ groups. There were significant differences (P<0.05). The ROC curve showed that the area under the curve (AUC) and 95％ CI of serum Copeptin, MMP-9, NT-proBNP and combinations of these three biomarkers in the diagnosis of CHF were 0.845 (0.781～0.914), 0.806 (0.736～0.883), 0.894 (0.828～0.962) and 0.925 (0.846～0.983) respectively, and the optimal thresholds were 12.5 pmol/L, 175.3 μg/L and 2037.0ng/L. The level of serum Copeptin was positively correlated with MMP-9 (r=0.807, P<0.001). Conclusion Serum Copeptin and MMP-9 may be involved in the ventricular remodeling in CHF children and they are expected to be a good indicator for the diagnosis of CHF and cardiac function.