肝素结合蛋白在急性呼吸窘迫综合征中的意义

The role of heparin-binding protein in acute respiratory distress syndrome

目的探讨导致血管渗漏的细胞因子肝素结合蛋白（heparin-bindingprotein，HBP） 在脓毒症相关急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）发病过程中起到的作用，并评价HBP水平对ARDS的预测价值。方法本前瞻性调查研究共纳入符合脓毒症诊断标准患者67例，根据是否出现ARDS分为ARDS组及非ARDS组。收集患者明确脓毒症诊断2 h内动脉血，留取血清ELISA法检测白介素（interleukin, IL）-6、IL-8以及HBP水平，统计中性粒细胞水平，并进行急性生理与慢性健康评分系统Ⅱ评分。根据方差齐性进行t或t’检验比较两组之间IL-6、IL-8、中性粒细胞水平以及HBP的差异；使用Spearman相关检验对HBP与其他三项指标进行分析；建立受试者工作特征曲线并计算曲线下面积以分析HBP对脓毒症相关ARDS的预测价值。结果ARDS组患者（32例）与非ARDS组（35例）患者比较，IL-6（t=4.25,P〈0.01）、IL-8（t=10.10,P〈0.01）、中性粒细胞（t=3.47,P=0.000 9）以及HBP（t=0.022 5,P=2.336）, IL-6（r=0.535,P=0.002）、IL-8（r=0.419,P=0.017）以及中性粒细胞（r=0.419,P=0.017）均与HBP呈正相关。HBP预测脓毒症相关ARDS曲线下面积为0.796。结论脓毒症相关ARDS发生时HBP水平升高，并与IL-6、IL-8水平以及中性粒细胞计数相关。HBP对预测脓毒症相关ARDS有较好的预测价值。HBP可能在脓毒症相关ARDS的发病中起到重要作用。IL-6、IL-8等炎症介质激活中性粒细胞，进而中性粒细胞释放HBP导致血管渗漏的病理过程可能ARDS是发病机制之一。

Objective To study the role of heparin-binding protein （HBP） in sepsis-associated acute respiratory distress syndrome （ARDS） , and to evaluate the prognostic value of HBP in ARDS. Method Sixty seven sepsis patients were enrolled in the prospective study. According to whether present ARDS, patients were divided into two groups： ARDS group and non-ARDS group. Blood samples were obtained within 2 hours after patients were diagnosed with sepsis. We measured the level of interleukin-6, interleukin- 8 and HBP by ELISA, counted the number of polymorphonuclear neutrophils （PMN）, and calculated Acute Physiology and Chronic Health Evaluation ]1 score. We compared interleukin-6, interleukin-8, PMN and HBP between two groups by Student＇ s t test. Correlation analysis was studied between HBP and other indicators by Spearman rank correlation coefficient. We also studied the early prognostic value on sepsis- associated ARDS by establishing receiver operating characteristic （ROC） curve. Results Interleukin-6 （t=4.25, P〈0. 01）, interleukin-8 （t=10.10, P〈0.01）, PMN （t=3.47, P=0.0009） and HBP （t = 0. 0225, P = 2. 336, all showed significant difference between ARDS group and non-ARDS group. Interleukin-6 （r=0.535, P=0.002）, interleukin-8 （r=0.419, P=0.017） and PMN （r=0.419, P = 0. 017） all had positive correlation with HBP. The area under curve （AUC） of HBP predicting ARDS was 0. 796. Conclusions HBP level elevated in sepsis-associated ARDS patients and were correlated with interleuki-6, interleuki-8 and PMN. HBP show a high value on predicting emergence of sepsis-associated ARDS. HBP may play an important role in sepsis-associated ARDS pathological process. From this study we can conclude one of possible ARDS pathogenesis： inflammatory mediators, such as interleuki-6, interleuki- 8, activate PMN. Subsequently PMN releases HBP. Then HBP results in vascular leakage, which is one of the basic ARDS pathology.