申麗華　張忠偉　朱　彪

(復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤學(xué)系-復(fù)旦大學(xué)附屬腫瘤醫(yī)院麻醉科重癥監(jiān)護(hù)室　上?！?00032)

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急性呼吸窘迫綜合征患者血清可溶性尿激酶型纖溶酶原激活物受體升高的意義

申麗華▲張忠偉▲朱彪△

(復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤學(xué)系-復(fù)旦大學(xué)附屬腫瘤醫(yī)院麻醉科重癥監(jiān)護(hù)室上海200032)

【摘要】目的通過測(cè)定急性呼吸窘迫綜合征 (acute respiratory distress syndrome,ARDS)患者及對(duì)照組的血清可溶性尿激酶型纖溶酶原激活物受體 (soluble urokinase-plasminogen activator receptor,su-PAR)水平,評(píng)估其診斷及判斷預(yù)后的價(jià)值。方法收集79例ARDS患者和30例心源性肺水腫 (cardiagenic pulmonary edema,CPE)患者,用酶聯(lián)免疫吸附測(cè)定法 (enzyme-linked immunosorbent assay,ELISA)測(cè)定su-PAR血清濃度。結(jié)果 ARDS患者血清su-PAR濃度顯著高于CPE組[10.42 (9.11～13.84) ng/mL vs.4.87 (3.35～9.61) ng/mL,P<0.001],在ARDS患者中存活組患者血清su-PAR濃度顯著低于非存活組[10.06 (8.48～11.96) ng/mL vs. 13.35 (10.08～16.65) ng/mL,P<0.001]。Logistic多元回歸分析顯示su-PAR(OR=1.52,P=0.034)是ARDS病例組30天死亡率的獨(dú)立預(yù)測(cè)因子。在ARDS組中取su-PAR最佳臨界點(diǎn)11.71 ng/mL,低于該值的患者30天死亡率明顯低于大于該值者 (P=0.005)。結(jié)論ARDS患者血清的su-PAR水平顯著高于CPE患者,su-PAR作為一個(gè)生物標(biāo)志物對(duì)ARDS和CPE患者的鑒別有一定的診斷價(jià)值。Su-PAR是ARDS患者短期死亡率的較強(qiáng)預(yù)測(cè)因子。

【關(guān)鍵詞】可溶性尿激酶型纖溶酶原激活物受體;急性呼吸窘迫綜合征;心源性肺水腫

急性呼吸窘迫綜合征 (acute respiratory distress syndrome,ARDS)是全世界范圍內(nèi)病死率極高的呼吸系統(tǒng)危重癥。其包括多種肺內(nèi)肺外病因:各種類型休克、感染、創(chuàng)傷、大量輸血、藥物中毒、胰腺炎和高危手術(shù)等。ARDS是由于彌漫性肺泡損傷導(dǎo)致肺泡毛細(xì)血管膜損傷、肺水腫及中性粒細(xì)胞的炎性反應(yīng)。輕度ARDS階段很多臨床表現(xiàn)與心源性肺水腫 (cardiagenic pulmonary edema,CPE)難于區(qū)分,而且診斷ARDS必須排除CPE,臨床常用的腦鈉素(berger nephropathy,BNP)及pro-BNP等心肌損傷標(biāo)志物也可為CPE的診斷提供依據(jù),但其對(duì)ARDS與CPE的鑒別仍有一定的局限性。臨床診斷最終要利用心動(dòng)超聲及侵入性的血流動(dòng)力學(xué)檢查來鑒別。目前國內(nèi)外對(duì)ARDS的生物信息研究較多[1],一些生物標(biāo)志物研究已經(jīng)取得了一定的進(jìn)展,如:基質(zhì)金屬蛋白酶 (matrix metallo proteinases,MMP)-1、-9，血管內(nèi)皮生長因子受體 (vascular endothelial growth factor receptor,VEGFR)-1、-2，血漿纖溶酶原激活物抑制劑-1 (plasminogen activator inhibitor-1,PAI-1)，腫瘤壞死因子 (tumor necrosis factor,TNF)-α,白介素 (interleukin,IL)-8、-12等。這些研究著重于炎性介質(zhì)參與的發(fā)病機(jī)制及信號(hào)轉(zhuǎn)導(dǎo)等方面,對(duì)ARDS和CPE的鑒別未能進(jìn)行系統(tǒng)的研究及指導(dǎo)。

近年來,su-PAR作為一種新型的炎性反應(yīng)標(biāo)志物受到關(guān)注,su-PAR是尿激酶型纖溶酶原激活物受體 (urokinase plasminogen activator receptor,uPAR) 的可溶形式,其由多種細(xì)胞分泌,包括中性粒細(xì)胞、淋巴細(xì)胞、單核細(xì)胞、巨噬細(xì)胞和內(nèi)皮細(xì)胞等[2]。su-PAR在血液和其他組織液中均可測(cè)量。su-PAR的血清水平較穩(wěn)定、無晝夜變化,且不受飲食的影響。它參與了多種免疫機(jī)制,包括細(xì)胞黏附、遷移、驅(qū)化、蛋白水解、免疫活化、組織重塑,侵襲和信號(hào)轉(zhuǎn)導(dǎo)。近年多項(xiàng)研究顯示,在低度炎癥、感染性疾病 (病毒、細(xì)菌和寄生蟲感染)、腫瘤、慢性肝病、慢性腎病中su-PAR水平升高,而且su-PAR水平越高,疾病的預(yù)后就越差。su-PAR與PAI-1共同參與了ARDS時(shí)肺內(nèi)的纖維蛋白相關(guān)炎癥[3-4]。鑒于su-PAR由炎癥刺激活化后的中性粒細(xì)胞所釋放的特性及趨化特性,及其在ARDS的纖維蛋白相關(guān)炎癥中的特殊作用,研究和分析su-PAR在ARDS患者血清中的水平有其重要的臨床意義。

本次研究目的在于尋找一個(gè)相對(duì)敏感的生物標(biāo)志物，不僅能夠?qū)RDS和CPE患者進(jìn)行早期識(shí)別，而且對(duì)ARDS的病情程度及預(yù)后的判斷也具有重要的指導(dǎo)意義。

資 料 和 方 法

研究對(duì)象選取2013年1月至2014年5月復(fù)旦大學(xué)附屬中山醫(yī)院ICU收治的所有109例ARDS和CPE患者。本次研究排除年齡<18歲,且未進(jìn)行抗凝及抗纖治療、未使用免疫抑制劑、無免疫缺陷病及未進(jìn)行血液透析治療者。所有患者均簽署知情同意書。

入組患者入ICU采血時(shí)未明確分組,采血后,根據(jù)現(xiàn)有的臨床信息、疾病進(jìn)展和治療反應(yīng)而最終診斷為ARDS或CPE。如果對(duì)診斷有異議,則進(jìn)一步超聲心動(dòng)圖或肺動(dòng)脈導(dǎo)管檢查,重新評(píng)估及討論后達(dá)成一致意見。ARDS的納入標(biāo)準(zhǔn)依據(jù)最新的柏林定義[5],CPE的診斷依據(jù)臨床征象 (奔馬律、頸靜脈擴(kuò)張、收縮期高血壓)及其他多種檢查:X線胸片 (心胸比>0.53,血管寬度>65 mm),心電圖 (新的ST段及T波改變)、實(shí)驗(yàn)室檢查 (肌鈣蛋白升高>0.1 ng/mL)、血流動(dòng)力學(xué)監(jiān)測(cè) [肺動(dòng)脈阻塞壓(pulmonary artery obstruction pressure,PAOP)≥18 mmHg,EF<45%,現(xiàn)存嚴(yán)重的心臟瓣膜病(主動(dòng)脈瓣或二尖瓣狹窄或返流),1 mmHg=0.133 kPa,下同],并對(duì)適當(dāng)?shù)闹委?(減輕前后負(fù)荷,局部缺血的治療或改善心肌收縮力的治療)有反應(yīng)[6]。

資料采集患者入ICU后進(jìn)行初次臨床評(píng)估,根據(jù)醫(yī)師的診斷及治療情況酌情進(jìn)行檢查，包括有創(chuàng)的血流動(dòng)力學(xué)監(jiān)測(cè),超聲心動(dòng)圖,肺功能,CT血管造影等。未能確診的患者置入Swan-Ganz進(jìn)行監(jiān)測(cè)。機(jī)械通氣的患者容量控制通氣時(shí),平臺(tái)壓<35 cmH2O,根據(jù)PaCO2水平調(diào)節(jié)呼吸頻率和潮氣量;壓力控制通氣時(shí),潮氣量不超過10 mL/kg。保持PaO2>60 mmHg,調(diào)整PEEP≥5 cmH2O。所有患者在入ICU后10 h內(nèi)做出ARDS或CPE的診斷。在病例入組后記錄并發(fā)癥、機(jī)械通氣資料、血流動(dòng)力學(xué)指標(biāo)和實(shí)驗(yàn)室檢查結(jié)果,并計(jì)算出APACHEⅡ、LPS和SOFA評(píng)分。根據(jù)病因把ARDS組分為感染組 (病因是感染因素)和非感染組 (所有其他病因:誤吸、創(chuàng)傷、多次輸血、失血性休克、心跳驟停后復(fù)蘇)。記錄從入組到以30天為事件終點(diǎn)隨訪病例的生存狀態(tài)。

標(biāo)本采集檢測(cè)所有的入組病例采集5 mL血液,在1 h內(nèi)4 ℃下離心 (2 500×g,10 min),取上清液凍存-80 ℃冰箱集中檢測(cè)。用ELISA測(cè)定血清su-PAR的濃度,按照試劑盒 (美國R&D公司)說明書進(jìn)行。

結(jié)果

一般資料共有109例病例入組,包括79例ARDS患者和30例CPE患者。ARDS病因包括肺炎38例(48.1%),非肺炎性膿毒癥21例 (26.6%),失血性休克8例 (10.1%),誤吸6例 (7.6%),心跳驟停后復(fù)蘇4例 (5.1%)和多次輸血導(dǎo)致者2例 (2.5%)。CPE的病因包括充血性心衰13例 (43.3%),心梗/心肌缺血9例 (30.0%),急性容量超負(fù)荷8例 (26.7%)。

根據(jù)最終的診斷分組病例特征及分層情況如表1。與ARDS組相比,CPE組患者有房顫病史者更多,氧合指數(shù)PO2/FiO2相對(duì)更高。超聲心動(dòng)圖和血流動(dòng)力學(xué)數(shù)據(jù)顯示CPE組患者左室射血分?jǐn)?shù)(leftventricularejectionfraction,LVEF)更低,而肺動(dòng)脈閉塞壓PAOP更高。

表1　ARDS和 CPE兩組患者的一般資料

(續(xù)表1)

ARDS:Acute respiratory distress syndrome;CPE:Cardiogenic pulmonary edema;BMI:Body mass index;APACHE Ⅱ:Acute physiology and chronic health evaluation Ⅱ;SOFA:Sequential organ failure assessment;PO2/FiO2:A ratio of arterial oxygen partial pressure and inspiratory oxygen fraction;LVEF:Left ventricular ejection fraction;PAOP:Pulmonary artery obstruction pressure;SvO2:Oxygen saturation of venous blood;APTT:Activated partial thromboplastin time;su-PAR:Soluble urokinase-type plasminogen activator receptor.Data were presented as median (interquartile range) for continuous variables and number (%) for categorical variables.1 mmHg=0.133 kPa.

su-PAR測(cè)定水平ARDS組患者的su-PAR水平顯著高于CPE組[10.42 (9.11～13.84) ng/mLvs. 4.87 (3.35～9.61) ng/mL,P<0.001]。以su-PAR水平診斷ARDS和CPE,計(jì)算ROC曲線下面積為0.821±0.049 (圖1)。最佳閾值>6.43 ng/mL時(shí),su-PAR診斷ARDS的敏感性為88.6%,特異性為66.7%。ARDS組患者分為感染組55例 (69.6%),非感染組24例 (30.4%)。Su-PAR水平分別為10.23 (8.74～14.38) ng/mL和10.49 (9.29～11.88) ng/mL,兩組間su-PAR水平差異無統(tǒng)計(jì)學(xué)意義 (P=0.444)。

ARDS組生存分析結(jié)果ARDS組患者死亡率為27.8%。非存活組與存活組相比,APACHEⅡ評(píng)分及SOFA評(píng)分及LIS評(píng)分顯著升高。而PO2/FiO2、動(dòng)脈血pH值、動(dòng)脈乳酸水平則降低,全組一 般情況結(jié)果見表2。死亡組的su-PAR水平與存活組相比顯著增高[13.35 (10.08～16.65) ng/mLvs. 10.06 (8.48～11.96) ng/mL,P=0.001]。而用su-PAR評(píng)價(jià)ARDS組的生存者和死亡者的30天存活率的ROC曲線下面積為0.703±0.071 (圖2)。預(yù)測(cè)死亡的最佳閾值為su-PAR>11.71 ng/mL,此最佳閾值診斷特異度可達(dá)71.9%,敏感度68.2%。隨訪患者30天存活情況,以su-PAR水平11.71 ng/mL為最佳閾值繪制Kaplan-Meier生存曲線 (圖3),低于此值者存活率與高于此值者差異有統(tǒng)計(jì)學(xué)意義 (P=0.005)。單變量Logistic回歸分析顯示動(dòng)脈血pH值、動(dòng)脈乳酸值、APACHEⅡ評(píng)分、SOFA評(píng)分、PO2/FiO2和血清su-PAR為ARDS組患者30天死亡率的共同預(yù)測(cè)因子,多變量Logistic回歸分析顯示在校正風(fēng)險(xiǎn)因子 (動(dòng)脈血pH值、動(dòng)脈乳酸值)后APACHEⅡ評(píng)分 (OR=1.196,P=0.016),SOFA評(píng)分 (OR=1.462,P=0.016),su-PAR (OR=1.258,P=0.003)和PO2/FiO2(OR=0.009,P=0.001 8)仍可作為死亡率的獨(dú)立預(yù)測(cè)因子。ARDS患者死亡率預(yù)測(cè)Logistic回歸分析結(jié)果見表3。

(續(xù)表2)

ARDS:Acute respiratory distress syndrome;BMI:Body mass index;APACHE Ⅱ:Acute physiology and chronic health evaluation Ⅱ;SOFA:Sequential organ failure assessment;LIS:Lung injury score;PO2/FiO2:A ratio of arterial oxygen partial pressure and inspiratory oxygen fraction;LVEF:Left ventricular ejection fraction;PAOP:Pulmonary artery obstruction pressure;SvO2:Oxygen saturation of venous blood;APTT:Activated partial thromboplastin time;su-PAR:Soluble urokinase-type plasminogen activator receptor.Data were presented as median (interquartile range) for continuous variables and number (%) for categorical variables.1 mmHg=0.133 kPa.

討論

早期識(shí)別輕度的ARDS與CPE有利于選擇更合理的治療方案。有很多方法可用于輕度ARDS和CPE的早期診斷,如:心動(dòng)超聲、血流動(dòng)力學(xué)監(jiān)測(cè)、BAL等。近年來一些生物標(biāo)志物的檢測(cè)對(duì)輕度ARDS的診斷也提供了幫助,如:IL-6,IL-8,TNFR,SP-D,VEGF,MMP-9,PAI-1[7-11]等。本次研究檢測(cè)了一種新的炎癥標(biāo)志物su-PAR,它在ARDS中的價(jià)值和作用還有待于更深入的探究。我們?cè)贏RDS組及CPE組中測(cè)定su-PAR濃度發(fā)現(xiàn),su- PAR在ARDS組中顯著高于CPE組。目前大量的關(guān)于su-PAR的研究結(jié)果顯示,炎癥和感染時(shí)外周血su-PAR濃度增高。包括膿毒血癥、呼吸機(jī)相關(guān)肺炎、HIV感染、肺結(jié)核、肺炎雙球菌菌血癥[12-16]。Su-PAR在膿毒血癥的診斷價(jià)值不如其他傳統(tǒng)炎癥標(biāo)志物PCT及CRP,三者ROC曲線下面積分別為0.62,0.86和0.78[17]。本研究中su-PAR對(duì)ARDS診斷的ROC曲線下面積是0.821,說明su-PAR的血清濃度對(duì)CPE與ARDS的鑒別具有一定的價(jià)值。

表3　ARDS患者死亡率預(yù)測(cè)Logistic回歸分析

ARDS:Acute respiratory distress syndrome;OR:Odds ratio;APACHE Ⅱ:Acute physiology and chronic health evaluation Ⅱ;SOFA:Sequential organ failure assessment;PO2/FiO2:A ratio of arterial oxygen partial pressure and inspiratory oxygen fraction;su-PAR:Soluble urokinase-type plasminogen activator receptor.a:log-transformed.

Su-PAR和PAI-1是凝血-纖溶過程的產(chǎn)物,t-PA和u-PA可激活纖溶酶原成為纖溶酶。PAI-1是纖溶酶原激活物的內(nèi)源性抑制劑[18-20]。在ARDS時(shí)肺的血管內(nèi)凝血導(dǎo)致血管內(nèi)的血栓形成,而肺泡間隔內(nèi)纖溶被抑制、促凝活性被加強(qiáng),遷移到此的纖維蛋白沉積增加而導(dǎo)致肺纖維化加重,而有研究顯示uPAR和PAI-1在肺泡上皮細(xì)胞有表達(dá),它們?cè)谵D(zhuǎn)錄后水平影響纖溶和凝血,促進(jìn)了肺纖維化,因此在ARDS時(shí)進(jìn)行抗凝和纖溶是很成功的策略[4]。Ville等[21]評(píng)估ARDS、膿毒血癥和腎臟替代治療患者的su-PAR和PAI-1水平對(duì)死亡率的預(yù)測(cè)價(jià)值,認(rèn)為高濃度的su-PAR可預(yù)測(cè)纖維蛋白相關(guān)炎癥性疾病的死亡率。 Su-PAR同PAI-1一樣共同參與了ARDS的纖維蛋白相關(guān)的炎性反應(yīng)。PAI-1作為ARDS的生物標(biāo)志物已被認(rèn)可,su-PAR也可能成為一個(gè)新的ARDS的生物標(biāo)志物。

此外,su-PAR在ARDS發(fā)病機(jī)制中的中性粒細(xì)胞引發(fā)的炎性反應(yīng)中也起到了一定的作用[22]。在ARDS的發(fā)病中,中性粒細(xì)胞被激活,各種抗炎及促炎因子大量釋放,多種因子激發(fā)了su-PAR的釋放,即可由炎癥刺激活化的中性粒細(xì)胞釋放,也可由IL-1β、bFGF或VEGF等因子從內(nèi)皮細(xì)胞刺激釋放,還有PDGF-BB、bFGF或IL-1β可刺激血管平滑肌細(xì)胞釋放su-PAR[23]。生理?xiàng)l件下uPAR在單核細(xì)胞、巨噬細(xì)胞、中性粒細(xì)胞、血管內(nèi)皮細(xì)胞和活化T細(xì)胞上表達(dá)。在炎癥發(fā)生時(shí),細(xì)胞表面的uPAR表達(dá)增高,在磷脂酶或蛋白酶的水解作用下,uPAR從細(xì)胞表面脫落,釋放入外周循環(huán),成為可溶性u(píng)PAR,即su-PAR,檢測(cè)uPAR和su-PAR水平可以從一個(gè)側(cè)面反映細(xì)胞分子水平的病理變化,uPAR因存在于細(xì)胞表面,取材受到一定限制,而su-PAR取材和檢測(cè)更為簡便,su-PAR的血清水平較穩(wěn)定、無晝夜變化,且不受飲食的影響。用su-PAR的檢測(cè)來研究疾病過程已成為一個(gè)重要方向。

進(jìn)一步對(duì)ARDS組患者隨訪30天的存活情況及對(duì)相關(guān)因素進(jìn)行分析后發(fā)現(xiàn),非存活組患者的PO2/FiO2更低,su-PAR濃度更高,病情更重。非存活組患者的ARDS的以中性粒細(xì)胞為核心的炎癥暴發(fā)反應(yīng)更加劇烈,導(dǎo)致肺泡上皮細(xì)胞及血管內(nèi)皮細(xì)胞損傷嚴(yán)重,致使氧合情況惡化,同時(shí)在相關(guān)因子刺激下su-PAR釋放增加,此外,低氧情況也可以進(jìn)一步導(dǎo)致su-PAR的表達(dá)增多,一些研究證實(shí)了這一點(diǎn)。Wojta等[24]研究發(fā)現(xiàn)低氧處理過的內(nèi)皮細(xì)胞uPA的活性下降。有研究發(fā)現(xiàn)[25-26],低氧條件下人微血管內(nèi)皮細(xì)胞 (human microvascular endothelial cells,hMVECs)的uPAR的表達(dá)增多,并且與其他類型的細(xì)胞如滋養(yǎng)層細(xì)胞、人臍靜脈血管內(nèi)皮細(xì)胞 (hUVECs)、乳腺癌細(xì)胞極其一致。在低氧條件下,uPAR的高表達(dá)和纖溶酶形成增多有助于hMVECs血管形成反應(yīng)的增強(qiáng)。研究還發(fā)現(xiàn),在uPAR的5’端區(qū)域有3個(gè)潛在的HIF-1的捆綁序列,表明低氧能夠直接影響uPAR的轉(zhuǎn)錄,或者低氧對(duì)基因轉(zhuǎn)錄的影響可能提高了uPAR表達(dá)的穩(wěn)定性。因此在ICU的ARDS患者中推廣su-PAR的檢測(cè),將有利于對(duì)患者病情的危重程度進(jìn)行判斷分層,從而對(duì)治療進(jìn)行有益的指導(dǎo)。

本研究用su-PAR預(yù)測(cè)ARDS組的30天死亡率的ROC曲線下面積是0.703。多元回歸分析顯示,su-PAR是一個(gè)對(duì)預(yù)后有著較強(qiáng)預(yù)示作用的因子。當(dāng)su-PAR>11.71 ng/mL時(shí),患者的死亡率顯著增加。而APACHEⅡ評(píng)分、SOFA評(píng)分、su-PAR和PO2/FiO2可作為死亡率的獨(dú)立預(yù)測(cè)因子。對(duì)比既往的研究,一項(xiàng)納入1914例膿毒血癥的前瞻性研究[27]結(jié)果顯示，su-PAR≥12 μg/L、APACHEⅡ≥17可作為膿毒血癥不良預(yù)后的獨(dú)立因素。Huttunen等[28]研究了132例菌血癥 (金黃色葡萄球菌、鏈球菌或大腸埃希菌引起)患者,su-PAR預(yù)測(cè)死亡的最佳閾值是11 ng/mL。隨訪30天時(shí)死亡18例，其中15例su-PAR>11 ng/mL,su-PAR在預(yù)測(cè)死亡上與SOFA評(píng)分相當(dāng)甚至更好。而在本研究中,su-PAR預(yù)測(cè)死亡較SOFA評(píng)分稍差,但其對(duì)死亡的預(yù)測(cè)作用與相關(guān)研究相符。

su-PAR作為一種新型的生物標(biāo)志物,對(duì)ARDS和CPE患者具有較好的鑒別診斷及對(duì)ARDS患者病情預(yù)測(cè)的價(jià)值,臨床上已有科研人員研制uPA/su-PAR結(jié)合抑制劑用于腫瘤的靶向治療,但其在疾病發(fā)生發(fā)展中的機(jī)制有待進(jìn)一步研究。su-PAR在ICU中對(duì)ARDS病情的診斷及判斷有極大的臨床應(yīng)用前景。

本研究存在一些局限,首先研究樣本量小,病種組成還不夠全面,取材有一定的局限;其次沒有同期測(cè)定肺泡液中su-PAR的濃度；最后沒有同期進(jìn)行其他生物標(biāo)志物測(cè)定。CPE的入組病例相對(duì)較少,可能會(huì)導(dǎo)致su-PAR對(duì)ARDS診斷的敏感性較高,特異度下降。

結(jié)語本研究對(duì)su-PAR是否可作為鑒別ARDS/ARDS和CPE患者的生物標(biāo)志物提供了依據(jù),su-PAR可作為ARDS/ARDS患者短期死亡的預(yù)測(cè)因子，其對(duì)ICU的ARDS患者的病情判斷有一定的指導(dǎo)意義和臨床應(yīng)用價(jià)值。

致謝復(fù)旦大學(xué)中山醫(yī)院ICU鄭逸雋醫(yī)師及相關(guān)醫(yī)護(hù)人員在病例樣本采集中提供了幫助。

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Increased plasma levels of soluble urokinase-type plasminogen activator receptor in patients with acute respiratory distress syndrome

SHEN Li-hua▲, ZHANG Zhong-wei▲, ZHU Biao△

(DepartmentofAnaesthesiaIntensiveCareUnit,ShanghaiCancerCenter-DepartmentofOncology,ShanghaiMedicalCollege,FudanUniversity,Shanghai200032,China)

【Abstract】ObjectiveTo assess the diagnostic and prognostic value of measuring soluble urokinase-plasminogen activator receptor (su-PAR) in acute respiratory distress syndrome (ARDS) patients.MethodsPlasma su-PAR was collected from 79 patients with ARDS and 30 patients with cardiogenic pulmonary edema (CPE) at enrollment.Levels of su-PAR were measured by ELISA.ResultsPatients with ARDS had significantly higher median levels of su-PAR compared with patients with CPE [10.42 (9.11-13.84) ng/mL vs. 4.87 (3.35-9.61) ng/mL,P<0.001] at enrollment.The su-PAR levels of survivors was significantly lower than that of non survivors [10.06 (8.48-11.96) ng/mL vs. 13.35 (10.08-16.65) ng/mL,P<0.001] in ARDS patients.Multivariate logistic regression showed that su-PAR (OR=1.52,P=0.034) was the independent predictor for 30-day mortality in patients with ARDS.The cut-off value of Su-PAR is 11.17 ng/mL in ARDS group.The mortality of 30 days in patients whoses value below 11.17 ng/mL is significantly lower than patients whose value exceed 11.17 ng/mL.ConclusionsPlasma su-PAR levels of ARDS patients were significantly higher than that of CPE patients.su-PAR as a biomarker is important in the differential diagnosis of patients with ARDS and CPE.su-PAR was a strong prognostic marker for short-term mortality in ARDS.

【Key words】soluble urokinase-type plasminogen activator receptor;acute respiratory distress syndrome;cardiagenic pulmonary edema

(收稿日期:2015-07-12;編輯:王蔚)

【中圖分類號(hào)】R181.3+2,R563.8

【文獻(xiàn)標(biāo)識(shí)碼】A

doi:10.3969/j.issn.1672-8467.2016.02.008

▲Co-first authors

△Corresponding authorE-mail:zhubiaozs@sohu.com