基质金属蛋白酶-9在川崎病早期诊断中的价值;白海涛

发布时间：2018-07-26 11:48

【摘要】：研究背景川崎病(Kawasaki Disease, KD)并发冠状动脉损伤是导致儿童后天性心脏病最主要的疾病，也是常见的血管炎症性疾病。早期诊断早期治疗，可以减少冠状动脉损伤的发生率。目前川崎病的诊断标准是以临床表现为主的排除性诊断，缺乏客观性诊断标准，，尤其是不完全川崎病（incomplete Kawasaki disease，iKD）患儿早期诊断相对困难，寻找可靠的血清学辅助诊断指标是目前研究的热点。基质金属蛋白酶-9(Matrix Metalloproteinase-9，MMP-9)参与了血管壁细胞外基质（Extracellular matrix，ECM）的降解过程，在血管炎症的过程中发挥着重要的作用。研究基质金属酶-9和川崎病之间的关系，可能为川崎病患儿的早期诊断带来帮助。目的通过观察川崎病发病早期的MMP-9血浆水平，了解它与川崎病之间的相关性，初步探讨它在川崎病诊断中的价值。方法对早期疑似川崎病的儿童入院后常规抽血，采用酶联免疫吸附法测量血浆MMP-9的水平，回顾性分析MMP-9在确诊川崎病组病例与过敏性紫癜组、发热组、健康对照组水平差异，同时分析在典型川崎病组与不完全川崎病组、冠状动脉扩张组与无冠状动脉扩张组水平差异；分析MMP-9与临床常用炎症反应指标血清降钙素原（Procalcitonin，PCT）、血沉（Erythrocyte Sedimentation Rate，ESR）、C反应蛋白（C-reactive proteinCRP）的相关性；以受试者工作曲线（ReceiverOperator Characteristive Curve，ROC曲线）分析MMP-9、ESR、CRP作为诊断是否川崎病的截断值（cutoff值）和相应的灵敏度和特异度，并比较曲线下面积，比较各指标的诊断优势。结果血浆MMP-9水平在川崎病早期明显升高，显著高于HSP组、感染组和健康对照组的水平，（ｐ＜0.05)。MMP-9的水平在典型和不完全川崎病之间没有显著性差异，而在冠状动脉扩张组的均值高于无冠状动脉扩张组，但差异没有显著性。ROC曲线结果显示MMP-9血浆值为90.23ng/mL的截断值时检测的灵敏度、特异度和曲线下面积,分别为83.3%、86.4%和0.904。以56.5mm/h为截断值时ESR的灵敏度、特异度和曲线下面积，分别为95.8%、66.1%和0.807。以27.55mg/L为截断值时CRP的灵敏度、特异度和曲线下面积,分别为83.3%、74.6%和0.789。统计分析显示MMP－9在川崎病诊断效能上优于CRP和ESR。结论 MMP-9在川崎病早期儿童中血浆水平明显升高，在截断值为90.23ng/mL诊断川崎病灵敏度和特异度较高，可作为川崎病儿童的早期辅助血清学检查的生物标记物。
[Abstract]:Background Kawasaki disease (Kawasaki disease) complicated with coronary artery injury (Kawasaki Disease, KD) is the leading cause of acquired heart disease in children and a common vascular inflammatory disease. Early diagnosis and early treatment can reduce the incidence of coronary artery injury. At present, the diagnostic criteria of Kawasaki disease are exclusion diagnosis, which is based on clinical manifestation, but lack of objective diagnostic criteria, especially the early diagnosis of incomplete Kawasaki disease (incomplete Kawasaki disease) is relatively difficult. It is a hot point to search for reliable serological diagnostic indexes. Matrix metalloproteinase-9 (MMP-9) is involved in the degradation of Extracellular matrix and plays an important role in the process of vascular inflammation. The study of the relationship between matrix metallozyme-9 and Kawasaki disease may be helpful for the early diagnosis of Kawasaki disease. Objective to investigate the relationship between MMP-9 plasma level and Kawasaki disease in the early stage of Kawasaki disease (Kawasaki disease) and to explore its value in the diagnosis of Kawasaki disease. Methods Plasma MMP-9 levels were measured by enzyme linked immunosorbent assay (Elisa) in early suspected Kawasaki disease (Kawasaki disease) children after admission. MMP-9 was analyzed retrospectively in Kawasaki disease group, Henoch-Schonlein purpura group and fever group. At the same time, the levels of coronary artery dilatation group and non-coronary artery dilatation group were compared between the typical Kawasaki disease group and the incomplete Kawasaki disease group. To analyze the correlation between MMP-9 and serum procalcitonin (PC), erythrocyte sedimentation rate (ESR), (Erythrocyte Sedimentation (Erythrocyte Sedimentation) C reactive protein (C-reactive proteinCRP). The sensitivity and specificity of MMP-9 ESR-CRP in Kawasaki disease (Kawasaki disease) were analyzed by using the (ReceiverOperator Characteristive curve (ROC curve). The area under the curve was compared and the diagnostic advantages of each index were compared. Results the plasma MMP-9 level was significantly higher in the early stage of Kawasaki disease than in the HSP group. There was no significant difference in the level of MMP-9 between typical and incomplete Kawasaki disease. However, the mean value of MMP-9 in the coronary artery dilatation group was higher than that in the non-coronary artery dilatation group, but there was no significant difference in .ROC curve. The sensitivity, specificity and area under the curve were 83.3% and 0.904%, respectively, when the plasma value of MMP-9 was truncated by 90.23ng/mL. The sensitivity, specificity and area under the curve of 56.5mm/h were 95.8% and 0.807%, respectively. The sensitivity, specificity and area under the curve of 27.55mg/L were 74.6% and 0.789%, respectively. Statistical analysis showed that MMP-9 was superior to CRP and ESR in the diagnosis of Kawasaki disease. Conclusion the plasma level of MMP-9 in children with Kawasaki disease was significantly higher than that in children with Kawasaki disease, and the sensitivity and specificity of 90.23ng/mL in the diagnosis of Kawasaki disease were higher than those in the truncated value, which could be used as a biomarker for early serological examination in children with Kawasaki disease.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.4

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