血清和脑脊液中MMPs与TIMP-1在重症手足口合并脑炎患儿中的诊断意义

The significance of mmps,timp-1 levels in serum and cerebrospinal fluid of children with severe hand-foot-mouth disease combined with encephalitis

目的探讨重症手足口合并脑炎患儿血清及脑脊液中MMPs与TIMP-1变化,为重症手足口合并脑炎患儿早期诊断提供依据。方法以2015-01—2018-03于郑州儿童医院就诊确诊为手足口患儿100例为研究对象,其中普通型55例,重型22例,危重型23例,其中重型及危重型HFMD组均为合并神经系统受累的患儿,统称为脑炎组。统计分析患儿脑脊液蛋白、脑脊液细胞数水平及脑脊液和血清中MMP-2、MMP-9、TIMP-1水平。结果(1)重型和危重型HFMD血清和脑脊液MMP-2、MMP-9、TIMP-1水平较普通型和健康对照组显著增高,危重型增高较为显著,差异有统计学意义(P<0.05);(2)脑炎组血清MMP-2、MMP-9、TIMP-1浓度水平较普通型、健康对照组组显著增高(P<0.05);(3)相关性分析结果显示,HFMD患儿血清MMP-2、MMP-9、TIMP-1浓度水平和脑脊液MMP-2、MMP-9、TIMP-1浓度水平显著正相关,相关系数分别为(r=0.719,P=0.001;r=0.638,P=0.000;r=0.704,P=0.000);(4)血清MMP-2、MMP-9和TIMP-1浓度水平预测脑炎ROC分析,曲线下面积分别为0.95695%CI(0.919、0.994)、0.95195%CI(0.906、0.996)、0.88795%CI(0.852、0.949),最佳截断点分别为103.59、96.34、108.64,相应敏感度和特异度分别为84.4%和94.5%、93.3和87.3%、88.9%和72.7%。结论重型和危重型HFMD合并神经系统受累病例血清和脑脊液中MMP-2、MMP-9、TIMP-1水平升高明显,对于重症手足口病合并脑炎的辅助诊断在临床上具有重要的意义。

Objective To investigate the changes of MMP and TIMP-1 tissue inhibitors in serum and cerebrospinal fluid of children with severe hand-foot-mouth encephalitis,and to provide basis for early diagnosis of children with severe hand-foot-mouth encephalitis.Methods 100 cases of hand,foot and mouth children diagnosed in our hospital from January 2015 to March 2018 were selected as research objects,including 55 cases of normal type,22 cases of severe type and 23 cases of critical type.Among them,the severe and critical type HFMD group were all children with neurological involvement,which were collectively referred to as the encephalitis group.The levels of CSF protein,CSF cell number and mmp-2,mmp-9 and timp-1 in CSF and serum were statistically analyzed.Results The levels of MMP-2,MMP-9 and TIMP-1 in serum and cerebrospinal fluid of heavy and critical HFMD were significantly higher than those of normal and healthy control groups,and the increase of critical HFMD was significant,with statistically significant difference(P<0.05).Serum levels of MMP-2,MMP-9 and TIMP-1 in the encephalitis group were significantly higher than those in the normal and healthy control groups(P<0.05).Correlation analysis results showed that serum MMP-2,MMP-9 and TIMP-1 concentrations of HFMD children were significantly positively correlated with cerebrospinal fluid concentrations of MMP-2,MMP-9 and TIMP-1,with correlation coefficients of(r=0.719 and P=0.001;R=0.638,P=0.000;R=0.704,P=0.000).ROC analysis of serum MMP-2,MMP-9 and TIMP-1 concentrations predicted encephalitis showed that the area under the curve was 0.956(95%CI(0.919,0.994)),0.951(95%CI(0.906,0.996)),and 0.887(95%CI(0.852,0.949)),and the optimal cut-off points were 103.59,96.34,and 108.64,respectively,with corresponding sensitivity and specificity of 84.4%and 94.5%,93.3 and 87.3%,88.9%and 72.7%,respectively.Conclusion The levels of MMP-2,MMP-9 and TIMP-1 in serum and cerebrospinal fluid of severe and critical HFMD patients with neurological involvement were significantly increased,which has important clinical significance for the auxiliary diagnosis of severe HFMD patients with encephalitis.