全身炎症反应综合征中血浆尿激酶型纤溶酶原激活物及其受体的表达

The expression of uPA and uPAR in patients with systemic inflammatory response syndrome

目的探讨upA，uPAR与D-D，IL-6及TNF-α之间的关系及其在SIRS中的作用。方法采用前瞻性、临床病例对照研究，病例的收集均来源于武汉市中心医院2008年1月至2010年1月年龄〉55岁的就诊患者，标本的采集均为清晨空腹静脉血清，检测全身炎症反应综合征（SIRS）患者血中尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）、D-二聚体（D-D）、白细胞介素6（IL-6）和肿瘤坏死因子（TNF-d）含量。按SIRS诊断标准分为SIRS组：50例来源于重症医学科；非SIRS组35例来源于内科病房；另选30例体检科体检者作为健康对照组，均需排除：（1）孕产妇；（2）恶性肿瘤；（3）转入ICU后7d内死亡；（4）心肺复苏术后；（5）既往有血液系统疾病；（6）人住ICU时即有SIRS的患者。采用双抗体夹心酶联免疫吸附法（ELISA）测定血中uPA，uPAR，D-D，IL-6及TNF-α含量。数据均采用SPSS17．0统计学软件进行分析：正态分布的计量资料以均数±标准差（x±s）表示，独立样本t检验进行分析；非正态分布的计量资料以中位数表示，Mann-Whitney秩和检验；相关性分析采用Spearman秩相关检验；以24h血uPA、uPAR、IL-6和TNF-α作受试者工作特征曲线（ROC曲线），比较SIRS患者血uPA，uPAR，IL-6和TNF-α含量诊断MODS的应用价值。结果SIRS组患者血uPA，uPAR，D-D，IL-6及TNF-α含量较非SIRS组和健康对照组均显著升高（均P〈0．01）。uPA与IL-6、TNF-仪不相关，uPAR与IL-6，TNF-α呈正相关（分别为r=0．395，P：0．004；，=0．606，P〈0．01）。以uPA，uPAR，IL-6及TNF-α诊断MODS做ROC曲线，ROC曲线下面积（AUROC）分别为0．59，0．76，0．86，0．83。结论uPA和uPAR参与了SIRS患者凝血功能障碍的过程，但在SIRS中起作用的途径机制并不完全相同。uPAR在SIRS向MODS的发展过程中起着一定作用。

Objective To test plasma levels of uPA, uPAR , D-dimer, IL-6 and TNF-α, andobserve the relationships between uPA, uPAR and D-dimer, IL-6 , TNF-αin patients with SIRS. Methods A prospective, clinical case-control study was adopted. Cases were collected from our hospital in January 2008 to January 2010, and all were 〉 55 years of age. Venous blood samples were collected via routine venipuncture. Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS ： SIRS group collected from Intensive Care Unit （n = 50） and non SIRS group collected from medical ward （n = 35）. The control group comprised 30 unrelated healthy blood donors who visited the General Health Checkup Division at our hospital. Patients with （1） pregnant women; （2） cancer; （3） died after admitted into ICU in 7 days ; （4） after cardiopulmonary resuscitation ; （ 5 ） with previous blood system diseases ; （ 6 ） patients with SIRS before admitted into ICU were excluded from the study, uPA , uPAR, D-D, IL-6 and TNF-α in blood were detected by commercial enzyme-linked immunosorbent assay （ELISA） kits. The data was analyzed using SPSS versionlT. 0. Data accorded with normal distribution of measurement was expressed as mean ± standard, and analyzed by independent-samples t test; non-normal distribution of measurement data, expressed by median, was analyzed with Mann-Whitney test. Relationships between plasma levels of uPA, uPAR and D-dimer, IL-6 TNF-α were analyzed using Spearman rank correlation test. To compare with blood level of uPA, uPAR, IL-6 and TNF-α in SIRS patients in the application of diagnostic value of MODS, we constructed the receiver operating characteristic curve （ROC curve） for blood levels of uPA, uPAR, IL-6 and TNF-α in 24 h. Results The plasma levels of uPA , uPAR, D-dimer, IL-6 and TNF-αin patients of SIRS were obviously higher compared with non-SIRS and normal controls （ all P 〈 0. 01 ）. Correlation analysis showed that there was positive correlation between uPAR level and IL-6 level （r = 0. 395, P = 0. 004） ; there was positive correlation between uPAR level and TNF-alevel （ r = 0. 606, P 〈 0. 01 ）. There was no correlation between uPAR level and D-dimer level （ r = - 0. 069, P = 0. 632）. There was no correlation between uPA level and D-dimer, IL-6 or TNF-α （all P 〉 0. 05）. There ROC curve were made based on the abilities of uPAR, D-dimer, IL-6 and TNF-cdevels in 24 hours to diagnose MODS, and the ROC areas under the curves were 0.76, 0. 58, 0. 86, 0. 83 respectively. Conclusions These results demonstrate that uPA and uPAR play a major contributory role in patients with SIRS in the process of coagulation disorders, but the mechanism in SIRS is not the same. uPAR may play a central rolein the development of SIRS to MODS.