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肝素结合蛋白在急性呼吸窘迫综合征诊断中的临床应用价值
Clinical Value of Heparin Binding Protein in Diagnosis of Acute Respiratory Distress Syndrome
【作者】 王斌;
【导师】 方强;
【作者基本信息】 浙江大学 , 内科学(重症医学), 2017, 硕士
【摘要】 目的:采用酶联免疫吸附法检测肝素结合蛋白在急性呼吸窘迫综合征(ARDS)患者血液(血浆)中的表达水平,探讨定量检测肝素结合蛋白在临床中的诊断ARDS的应用价值,比较非ARDS患者、ARDS患者及严重ARDS患者血液中肝素结合蛋白与降钙素原、超敏C反应蛋白和IL-17在ARDS中的诊断意义。方法:采集20例健康志愿者,35例非ARDS患者,35例ARDS患者,35例严重ARDS患者的全血,采用酶联免疫吸附法(ELISA)对各实验组血浆进行肝素结合蛋白(heparin-bindingprotein,HBP)的定量测定,同时还结合了酶联荧光法检测血浆中的降钙素原(procalcitonin,PCT)水平、采用比浊法检测其中的超敏C反应蛋白(hs-CRP)水平,酶联免疫吸附法(ELISA)检测IL-17;将实验组和对照组血浆中各指标的检测结果进行统计、比较;绘制受试者操作特征曲线(receiver operating characteristic curve,ROC 曲线),并对曲线下的面积(area under the curve,AUC)进行计算,找出最佳的截断值,通过该值分析并比较HBP、PCT、hs-CRP和IL-17等在诊断ARDS时的灵敏度和特异度。结果:健康对照组、非ARDS组、ARDS组、严重ARDS组HBP各组间差异均有统计学意义(P<0.01);ARDS组和严重ARDS组、健康对照组和非ARDS组间差别均有统计学意义(P<0.01),严重ARDS组高于ARDS组,且组间差异有统计学意义(P<0.05),非ARDS组与ARDS组差别无统计学意义(P=0.32);PCT水平各组间差异均有统计学意义(P<0.01);hs-CRP各组间差异均有统计学意义(P<0.01);IL-17各组间差异均有统计学意义(P<0.01)。经ROC曲线分析显示HBP曲线下面积为0.772,且血浆中HBP浓度为11.5ng/m1时,其诊断ARDS的敏感度能达到76.1%,特异度高达78.8%。当HBP浓度达到19.6ng/m1时,其诊断严重ARDS的灵敏度为85.1%,特异度为89.8%。结论:血浆中HBP、PCT、hs-CRP和IL-17在临床上都可以作为ARDS的检测指标,且可以根据值的大小对患者病情进行评估。当HBP浓度达到30ng/m1时,其诊断严重ARDS的灵敏度和特异度分别为为85.1%和89.8%,可以作为ARDS良好的预警标志物,对于ARDS病情进展的监测作用很大。如果和患者血浆中的HBP,PCT和IL-17联合检测,对ARDS的预测效果更好。
【Abstract】 Objective:Observation of heparin binding protein in acute respiratory distress syndrome(ARDS)expression levels in the plasma of patients,to explore the clinical application value of heparin binding protein detection in the diagnosis of ARDS,heparin binding protein and calcitonin peptide and the diagnostic significance of high sensitive C reactive protein and IL-17 in ARDS.Method:The acquisition of 20 healthy volunteers,35 patients with non ARDS patients,35 cases of ARDS,the blood of 35 patients with severe ARDS,using enzyme-linked immunosorbent assay for quantitative detection of plasma heparin binding protein(heparin-binding protein,HBP),at the same time using enzyme-linked fluorescent assay of procalcitonin(procalcitonin,PCT),the particle reinforced the immune turbidimetric method for detection of high sensitive C reactive protein(hs-CRP)level,enzyme-linked immunosorbent assay(ELISA)detection of IL-17.The statistics and comparison of healthy volunteers and non physical differences in level of the detection of ARDS patients,ARDS patients and ARDS patients with severe plasma;draw the receiver operating characteristic curve(ROC curve)and calculate the area under the curve,to find the optimal cut-off value,analysis and comparison of HBP,PCT,hs-CRP and IL-17 sensitivity and when the specificity in diagnosis of ARDS.Result:The healthy control group and non ARDS group,ARDS group,HBP group of severe ARDS groups both had significant difference(P<0.01);control group and non ARDS group,ARDS group and severe ARDS group the difference were statistically significant(P<0.01),severe ARDS group than in ARDS group,the difference was statistically significant(P<0.01),non ARDS group and ARDS group had no significant difference(P=0.45);the level of PCT between groups differences were statistically significant(P<0.01);hs-CRP group differences were statistically significant(P<0.01);IL-17 group differences were statistically significant(P<0.01).ROC curve analysis showed that the area under the HBP curve(area under the curve,AUC)was 0.772,and the sensitivity and specificity of the diagnostic ARDS were up to 76.1%when the plasma HBP concentration was about 11 ng/ml.When HBP concentration reached 30ng/ml,the sensitivity of the diagnosis of severe ARDS was 85.1%and specificity was about 89.8%.Linear correlation analysis showed that the plasma PCT was positively correlated with HBP(r=0.874,P<0.01),no linear correlation with hs-CRP(r=0.47,P=0.133),and the plasma levels of HBP and hs-CRP also have no linear correlation(r=0.58,P=0.203).Conclusion:Plasma HBPm PCT,hs-CRP and IL-17 can be used as indicators of ARDS detection,and can be used for disease severity assessment.When the HBP concentration reached 30ng/ml,the sensitivity of diagnosis of severe ARDS was 85.1%,the specificity was 89.8%,ARDS is better early warning biomarkers can be used in monitoring the disease activity of ARDS.Combined detection of plasma HBP,PCT and IL-17 analysis of their correlation,can better predict the occurrence of ARDS.
【Key words】 ARDS; heparin binding protein; procalcitonin; high sensitivity C reactive protein; interleukin 17;