薛力瑋， 劉 穎

1.桂林醫(yī)學(xué)院，廣西 桂林 541001； 2．桂林醫(yī)學(xué)院第二附屬醫(yī)院消化科

紅細(xì)胞分布寬度對(duì)急性胰腺炎嚴(yán)重程度和預(yù)后評(píng)估的價(jià)值

薛力瑋1， 劉 穎2

1.桂林醫(yī)學(xué)院，廣西 桂林 541001； 2．桂林醫(yī)學(xué)院第二附屬醫(yī)院消化科

目的探討紅細(xì)胞分布寬度(red blood cell distribution width, RDW)水平及入院后其動(dòng)態(tài)變化對(duì)急性胰腺炎(acutepancreatitis, AP)病情預(yù)后的評(píng)估價(jià)值。方法選擇2010年1月至2017年6月在桂林醫(yī)學(xué)院附屬醫(yī)院收治的AP患者120例，設(shè)輕癥組(MAP，43例)、中-重癥組(MSAP，32例)及重癥組(SAP，45例)；根據(jù)是否診斷為SAP組，分為非SAP組(75例)和SAP組(45例)；再將SAP組分為生存組(25例)、死亡組(20例)；對(duì)照組為健康體檢者(30名)。收集患者入院時(shí)RDW、入院48 h后RDW、對(duì)照組RDW及其他相關(guān)臨床資料，比較各組間RDW的差異、RDW的動(dòng)態(tài)變化、RDW與APACHEⅡ評(píng)分、Ranson評(píng)分的相關(guān)性，利用受試者工作特征曲線(ROC)并確定曲線下面積(AUC)來(lái)分析RDW對(duì)AP的嚴(yán)重程度和預(yù)后的價(jià)值。結(jié)果SAP組入院時(shí)RDW及入院48 h后RDW均明顯高于其他三組(P<0.001)；SAP組及MSAP組中，入院48 h后RDW與入院時(shí)RDW變化不大(P>0.05)；在多因素 Logistic 回歸分析中，入院時(shí)RDW、APACHEⅡ評(píng)分、Ranson評(píng)分等指標(biāo)均為SAP診斷及院內(nèi)死亡的獨(dú)立危險(xiǎn)因素(P<0.05)；入院時(shí)RDW對(duì)診斷SAP的預(yù)測(cè)價(jià)值ROC曲線分析顯示，RDWAUC為0.953(95%CI：0.899～0.983，P<0.001)；根據(jù)約登指數(shù)計(jì)算出入院時(shí)RDW最佳臨界值為13.9%，敏感度為95.56%，特異度為81.33%；入院時(shí)RDW對(duì)SAP院內(nèi)死亡的預(yù)測(cè)價(jià)值ROC曲線分析顯示，RDWAUC為0.849(95%CI: 0.711～0.938，P<0.001)；根據(jù)約登指數(shù)計(jì)算出入院時(shí)RDW最佳臨界值為16.2%，敏感度為70.00%，特異度為92.00%。結(jié)論RDW可預(yù)測(cè)AP的嚴(yán)重程度和預(yù)后，同時(shí)RDW的動(dòng)態(tài)變化對(duì)AP的病情可能具有較好的預(yù)測(cè)價(jià)值。

紅細(xì)胞分布寬度；急性胰腺炎；預(yù)后評(píng)估

急性胰腺炎(acute pancreatitis,AP)按病情嚴(yán)重程度，可分為輕癥胰腺炎(mild acute pancreatitis, MAP)、中-重癥胰腺炎(moderately severe acute pancreatitis, MSAP)、重癥胰腺炎(severe acute pancreatitis, SAP)[1]。大多數(shù)AP常呈自限性，預(yù)后良好，但在SAP中，由于胰腺酶進(jìn)入血液和隨后造成對(duì)各個(gè)器官的損傷，在器官損傷后，會(huì)釋放大量炎癥介質(zhì)和細(xì)胞因子，疾病早期即可引起系統(tǒng)性并發(fā)癥，如全身炎癥反應(yīng)綜合征(systemic inflammatory response syndrome, SIRS)和多器官功能障礙綜合征(multiple organ dysfunction syndrome, MODS)，嚴(yán)重AP的死亡率為36%～50%[2]。因此, 在入院后24～48 h內(nèi)評(píng)估AP患者嚴(yán)重程度和預(yù)后對(duì)AP的早期治療非常重要。

紅細(xì)胞分布寬度(red blood cell distribution width, RDW)可反映紅細(xì)胞的異質(zhì)性。目前許多研究[3-7]已證實(shí)，RDW在各種疾病中可作為一個(gè)獨(dú)立、強(qiáng)大的預(yù)后及并發(fā)癥的預(yù)測(cè)指標(biāo)，如心血管疾病、腦卒中、呼吸系統(tǒng)疾病及2型糖尿病。enol等[8]第一次證明了RDW是AP死亡的獨(dú)立危險(xiǎn)因素之一，但其機(jī)制尚不明確。本研究通過(guò)分析AP患者早期RDW 水平與RDW 動(dòng)態(tài)變化，評(píng)估RDW對(duì)AP嚴(yán)重程度和預(yù)后評(píng)估的價(jià)值，并探討其機(jī)制。

1 資料與方法

1.1一般資料選擇2010年1月至2017年6月在桂林醫(yī)學(xué)院附屬醫(yī)院收治AP患者120例，研究對(duì)象符合中華醫(yī)學(xué)會(huì)外科學(xué)分會(huì)胰腺外科學(xué)組《急性胰腺炎診治指南》(2014年)的診斷標(biāo)準(zhǔn)[1]；按病情嚴(yán)重程度分為MAP組(43例)、MSAP組(32例)、SAP 組(45例)；根據(jù)是否診斷為SAP組，分為非SAP組(75例)和SAP組(45例)；再將SAP組分為生存組(25例)、死亡組(20例)；120例患者中，男82例、女38例，年齡(53.83±16.95)歲(21～89歲)；對(duì)照組為健康體檢者30名，男19名、女11名，年齡(46.70±16.43)歲(22～74歲)。

1.2方法收集患者入院時(shí)RDW、入院48 h后RDW、對(duì)照組RDW及其他相關(guān)臨床資料，統(tǒng)計(jì)SAP患者住院期間病死率。

2 結(jié)果

2.1入院時(shí)RDW比較120例AP患者入院時(shí)RDW明顯高于對(duì)照組；MSAP組入院時(shí)RDW明顯高于MAP組；SAP組入院時(shí)RDW明顯高于MSAP組；但MAP組入院時(shí)RDW值與對(duì)照組的RDW值比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表1)。

2.2入院48h后RDW動(dòng)態(tài)變化情況MAP組中入院48 h后RDW明顯低于入院時(shí)RDW(P<0.001)；MSAP、SAP組中入院48 h后RDW與入院時(shí)RDW比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表1)。

表1 入院時(shí)與入院48 h后各組RDW值比較Tab 1 Comparison of RDW values at the time of admission and 48 hours after admission (±s)

注：與SAP組相比，*P<0.05;與MSAP組相比，#P<0.05。

2.3不同性別、病因AP患者RDW比較MAP組、MSAP組和SAP組內(nèi)不同性別、病因入院時(shí)RDW比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；MAP組、MSAP組和SAP組內(nèi)不同性別、病因入院48 h后RDW比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表2)。

2.4RDW與APACHEⅡ評(píng)分、Ranson評(píng)分的相關(guān)性入院時(shí)RDW與APACHE Ⅱ評(píng)分、Ranson評(píng)分均存在良好的相關(guān)性，相關(guān)系數(shù)r值分別為0.778、0.678；入院48 h后RDW與APACHE Ⅱ評(píng)分、Ranson評(píng)分均存在良好相關(guān)性，相關(guān)系數(shù)r值分別為0.794、0.716。

2.5SAP組和非SAP組中臨床資料比較年齡、入院時(shí)RDW、APACHE Ⅱ評(píng)分、Ranson評(píng)分在兩組間比較，差異均有統(tǒng)計(jì)學(xué)意義(P<0.001，見(jiàn)表3)。Logistic 回歸多因素分析顯示：入院時(shí)RDW、APACHE Ⅱ評(píng)分、Ranson評(píng)分均為診斷SAP的獨(dú)立危險(xiǎn)因素(P<0.05)；在對(duì)診斷SAP預(yù)測(cè)價(jià)值ROC曲線分析顯示，RDWAUC為0.953(95%CI: 0.899～0.983，P<0.001)；根據(jù)約登指數(shù)計(jì)算出入院時(shí)RDW最佳臨界值為13.9%，靈敏度為95.56%，特異度為81.33%(見(jiàn)圖1)；APACHE Ⅱ評(píng)分AUC為0.932 (95%CI: 0.871～0.970，P<0.001)；Ranson評(píng)分AUC為0.898 (95%CI: 0.830～0.946，P<0.001)。

2.6生存組和死亡組中臨床資料比較入院時(shí)RDW、APACHE Ⅱ評(píng)分、Ranson評(píng)分在兩組間比較，差異均有統(tǒng)計(jì)學(xué)意義(P<0.001，見(jiàn)表4)。Logistic回歸多因素分析顯示：入院時(shí)RDW、APACHE Ⅱ評(píng)分、Ranson評(píng)分均為SAP院內(nèi)死亡的獨(dú)立危險(xiǎn)因素(P<0.05)；在對(duì)SAP院內(nèi)死亡預(yù)測(cè)價(jià)值ROC曲線分析顯示，RDWAUC為0.849(95%CI: 0.711～0.938，P<0.001);根據(jù)約登指數(shù)計(jì)算出入院時(shí)RDW最佳臨界值為16.2%，靈敏度為70.00%，特異度為92.00%(見(jiàn)圖2)；APACHE Ⅱ評(píng)分AUC為0.945(95%CI: 0.833～0.991，P<0.001)；Ranson評(píng)分AUC為0.888(95%CI: 0.758～0.962，P<0.001)。

表2 不同性別、病因AP患者RDW比較Tab 2 Comparison of RDW of AP patients between different gender and pathogenesis (±s)

表3 SAP組與非SAP組中一般臨床資料比較Tab 3 Comparison of clinical characteristics between SAP group and non-SAP group (±s)

表4 生存組與死亡組中一般臨床資料比較Tab 4 Comparison of clinical characteristics between survival group and death group (±s)

圖1 RDW對(duì)SAP診斷預(yù)測(cè)價(jià)值的ROC曲線；圖2 RDW對(duì)SAP院內(nèi)死亡預(yù)測(cè)價(jià)值的ROC曲線Fig 1 ROC curve of RDW to predict the diagnosis of SAP; Fig 2 ROC curve of RDW to predict the hospital death of SAP

3 討論

AP既包括胰腺局部炎癥病變，也包括全身病理?yè)p傷。約20%的患者為SAP，常并發(fā) MODS或感染而死亡[2]。目前Ranson評(píng)分仍然是評(píng)估AP病情嚴(yán)重程度的最常用的評(píng)分系統(tǒng)，但這個(gè)評(píng)分系統(tǒng)需要在入院后48 h來(lái)完成評(píng)估，其余的如APACHEⅡ評(píng)分、BISAP評(píng)分、MCTSI評(píng)分涉及許多測(cè)試，而且操作復(fù)雜，所以對(duì)臨床實(shí)踐并不方便；而在實(shí)驗(yàn)室檢查中，肌酐、尿素氮特異性和靈敏性都有一定的局限性[9]；C反應(yīng)蛋白(CRP)水平具有較高的靈敏性和陽(yáng)性預(yù)測(cè)值，但CRP水平無(wú)法預(yù)測(cè)AP病情嚴(yán)重程度[10-11]；降鈣素原(PCT)聯(lián)合其他炎癥指標(biāo)，如白細(xì)胞介素-6(IL-6)，可預(yù)測(cè)AP炎癥嚴(yán)重程度[12]，乙酰膽堿酯酶(AChE)對(duì)評(píng)估AP病情嚴(yán)重程度也具有較強(qiáng)的靈敏性和特異性[13]，但都不在臨床常規(guī)檢測(cè)范圍內(nèi)；白細(xì)胞介素-8(IL-8)、尿胰蛋白酶原激活肽(uTAP)、腫瘤壞死因子(TNF-α)目前還沒(méi)有在臨床上應(yīng)用[9]。而RDW可反映全身系統(tǒng)的炎癥反應(yīng)，多項(xiàng)研究[8-9]證明，高水平RDW是對(duì)SAP患者死亡率的獨(dú)立預(yù)測(cè)因子。

本研究發(fā)現(xiàn)，SAP組入院時(shí)RDW及入院48 h后RDW均明顯高于MAP及MSAP組，在多因素 Logistic回歸分析中RDW、APACHEⅡ評(píng)分、Ranson評(píng)分等指標(biāo)均為SAP診斷及院內(nèi)死亡的獨(dú)立危險(xiǎn)因素，通過(guò)ROC曲線分析，RDW對(duì)AP嚴(yán)重程度及預(yù)后的靈敏性及特異性均較強(qiáng)。而在SAP組及SMAP組中，入院48 h后RDW與入院時(shí)RDW變化不大，考慮與AP局部或全身并發(fā)癥及器官功能衰竭有關(guān)，這也提示了RDW的動(dòng)態(tài)變化可能對(duì)AP嚴(yán)重程度及預(yù)后有預(yù)測(cè)價(jià)值。

據(jù)報(bào)道[8]，RDW的變化與疾病的炎癥狀態(tài)有關(guān)，這也許可以解釋為什么更高水平RDW值的AP患者病情更重、死亡率更高。炎性因子和氧化應(yīng)激在AP的發(fā)病和進(jìn)展中起至關(guān)重要的作用。胰腺腺泡細(xì)胞的損傷在AP早期導(dǎo)致局部炎癥反應(yīng)，之后腺泡細(xì)胞凋亡或壞死可導(dǎo)致SIRS及MODS[14]。若紅細(xì)胞生成時(shí)缺乏鐵、維生素B12、葉酸等造血原料時(shí)，相應(yīng)的RDW就會(huì)升高[15]。炎癥影響骨髓中紅細(xì)胞前體和鐵代謝，同時(shí)炎性細(xì)胞因子可破壞紅細(xì)胞細(xì)胞膜，抑制其成熟，讓更新、更大的網(wǎng)織紅細(xì)胞進(jìn)入循環(huán)， 從而使RDW升高[16]。炎癥可改變紅細(xì)胞膜糖蛋白和膜離子通道，使得紅細(xì)胞形態(tài)發(fā)生變化，導(dǎo)致紅細(xì)胞大小異質(zhì)性增加[17-18]。而氧化應(yīng)激可通過(guò)破壞核酸、蛋白及脂質(zhì)從而降低紅細(xì)胞存活率并讓更多未成熟紅細(xì)胞進(jìn)入血液循環(huán)[19]。此外，SAP常因全身血容量下降導(dǎo)致腎前性的急性腎損傷，同時(shí)長(zhǎng)時(shí)間腸外營(yíng)養(yǎng)及應(yīng)激狀態(tài)可導(dǎo)致貧血，從而使RDW升高[20]。因此，RDW值反映了AP的炎癥狀態(tài),可用于預(yù)測(cè)AP的嚴(yán)重程度和預(yù)后。

綜上所述,RDW可預(yù)測(cè)AP的嚴(yán)重程度和預(yù)后，初步解釋了其存在的機(jī)制，同時(shí)RDW的動(dòng)態(tài)變化對(duì)AP的病情也可能具有較好的預(yù)測(cè)價(jià)值，但本研究屬于回顧性分析, 存在樣本相對(duì)偏少,且未對(duì)AP患者出院后進(jìn)行隨訪，無(wú)法了解出院后RDW動(dòng)態(tài)變化情況的問(wèn)題，對(duì)研究結(jié)果難免造成偏差。此外，還需進(jìn)一步探究AP中RDW升高的具體機(jī)制。

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(責(zé)任編輯：李 健)

Valueofredbloodcelldistributionwidthinassessingtheseverityandprognosticevaluationofacutepancreatitis

XUE Liwei1, LIU Ying2

1.Guilin Medical University, Guilin 541001; 2.Department of Gastroenterology, the Second Affiliated Hospital of Guilin Medical University, China

ObjectiveTo explore the value of red blood cell distribution width (RDW) and its dynamic changes after admission in assessing the severity and prognostic evaluation of acute pancreatitis (AP).MethodsOne hundred and twenty cases of AP patients including 43 cases of mild acute pancreatitis (MAP), 32 cases of moderate severe acute pancreatitis (MSAP) and 45 cases of severe acute pancreatitis (SAP) from Jan. 2010 to Jun. 2017 in the Affiliated Hospital of Guilin Medical University were selected. According to the diagnostis of SAP or not， patients were divided into non-SAP group (75 cases) and SAP group (45 cases). Patients in SAP group were divided into survival group (25 cases) and death group (20 cases)， 30 healthy volunteers were selected as the control group. RDW of patients was collected at the time of admission and 48 hours after admission to hospital, as well as the RDW of the control group and other relevant clinical data were collected. The difference value of RDW in each group, the dynamic changes of the RDW and the correlation of RDW with APACHE Ⅱ score, Ranson score were compared. The value of RDW to the severity and prognosis of AP were analyzed by theROCcurve and area under curve (AUC).ResultsThe RDW of SAP group at the time of admission and 48 hours after admission to hospital were significantly higher than those in the other three groups (P<0.001). In the SAP group and MSAP group, the RDW at the time of admission was not significantly changed after 48 hours in hospital (P>0.05). In a multiariable Logistic regression analysis, RDW, APACHE Ⅱ score and Ranson score indexes at the time of admission were all independent risk factors for SAP diagnosis and hospital death (P<0.05). TheROCcurve analysis of the prediction value of SAP in admission showed that the RDWAUCwas 0.953 (95%CI: 0.899-0.983,P<0.001). According to the Youden index, the optimal critical value of RDW when admission was 13.9 % and the sensitivity was 95.56 % and the specificity was 81.33 %. RDW on admission to hospital to prognosis of death in the hospital in SAP group ofROCcurve analysis showed that RDWAUCwas 0.849 (95%CI: 0.711-0.938,P<0.001). According to the Youden index, the optimal critical value of RDW when admission was 16.2% and the sensitivity was 70.00% and the specificity was 92.00%.ConclusionRDW can predict the severity and prognosis of AP, and the dynamic change of RDW may have important value to predict the condition of it.

Red blood cell distribution width; Acute pancreatitis; Prognostic evaluation

10.3969/j.issn.1006-5709.2017.11.026

國(guó)家自然科學(xué)基金(81660097)

薛力瑋，在讀碩士研究生，研究方向：消化系統(tǒng)疾病。E-mail: xueliwei0528@126.com

劉穎，博士，副主任醫(yī)師，副教授，研究方向：胃腸動(dòng)力。E-mail: liuy1009@sina.com

R576

A

1006-5709(2017)11-1301-04

2017-07-13