急性胰腺炎患者IL-1β和sE-selectin含量的變化及其意義

胡端敏 周春華 王少峰

·論著·

急性胰腺炎患者IL-1β和sE-selectin含量的變化及其意義

胡端敏 周春華 王少峰

目的觀測急性胰腺炎(acute pancreatitis，AP)患者外周血清白介素-1β(interleukin-1β,IL-1β)和可溶性E-選擇素(soluble E-selectin,sE-selectin)水平的變化，探討其對AP病情嚴重程度判斷的價值。方法41例AP患者分為重癥急性胰腺炎組(SAP，19例)和輕癥急性胰腺炎組(MAP，22例)，于入院后1、3、7、14 d采集血清，以ELISA 法檢測血清IL-1β和sE-selectin水平。另選擇20例健康者作為對照。結(jié)果對照組血清IL-1β濃度為(18.71±2.43)ng/L；MAP組1、3、7 d分別為(61.18±7.47)ng/L、(33.03±5.85)ng/L、(20.73±4.07)ng/L； SAP組1、3、7、14 d分別為(86.91±13.32)ng/L、(81.35±12.71)ng/L、(64.93±5.99)ng/L、(21.40±49.13)ng/L。SAP組入院后1、3、7 d的IL-1β濃度較對照組和MAP組均顯著升高(P<0.05 ),14 d與對照組無顯著差異。對照組血清sE-selectin濃度為(10.69±2.51)ng/ml；MAP組1、3、7 d分別為(41.60±6.85)ng/ml、(14.90±3.51)ng/ml、(9.85±2.88)ng/ml；SAP組1、3、7、14 d分別為(84.73±15.37)ng/ml、(95.65±13.06)ng/ml、(39.41±3.73)ng/ml、(12.25±2.29)ng/ml。SAP組入院后1、3、7 d的sE-selectin濃度較對照組和MAP組均顯著升高(P<0.05 )，14 d與對照組無顯著差異。AP患者入院第1天的血清IL-1β含量和sE-selectin含量存在正相關(guān)關(guān)系(r=0.851，P<0.01)。結(jié)論AP患者血清IL-1β和sE-selectin的檢測有助于判斷病情的嚴重程度。

胰腺炎； 白細胞介素-1β； E-選擇素

目前研究認為，急性胰腺炎(AP)時細胞因子的過量產(chǎn)生誘發(fā)細胞黏附分子(cell adhesion molecules，CAMs)的表達，引起白細胞的滾動、吸附、侵入和滲出，進而引發(fā)器官損害。其中內(nèi)皮細胞表達的E-選擇素(E-selectin)通過與白細胞相應受體的結(jié)合導致了白細胞在毛細血管后靜脈的滾動，然后幫助其遷移入組織[1]。本文動態(tài)觀測AP患者外周血清可溶性E-selectin(sE-selectin)和IL-1β水平的變化，探討它們與AP病情進展及預后的關(guān)系。

資料與方法

一、臨床資料

收集蘇州大學附屬第一、二醫(yī)院2007年6月至2009年2月收治的41例住院AP患者，其中男21例，女20例，年齡39～80歲，平均(60±12)歲。根據(jù)2004年中華醫(yī)學會消化病學分會胰腺病學組制定的臨床診斷及輕癥急性胰腺炎(mild acute pancreatitis，MAP)和重癥急性胰腺炎(severe acute pancreatitis，SAP)分類標準[2]，MAP 22例，SAP 19例；膽源性28例，高血脂性7例，酒精性3例，特發(fā)性3例。所有SAP患者APACHEⅡ評分均≥8分，CT分級均為D級或E級。另選蘇州大學附屬第二醫(yī)院健康體檢未發(fā)現(xiàn)器質(zhì)性疾病者20名作為對照組，男11例，女9例，年齡28～56歲，平均(42±11)歲。

二、標本的采集與處理

于入院第1、3、7、14(僅SAP組)d抽取外周靜脈血3 ml，離心取血清。同樣取對照組血，分離血清。均置-20℃保存。

三、血清IL-1β和sE-selectin的檢測

采用ELASA方法。試劑盒購自博士德公司，按說明書操作，最后用酶標儀測A450值。以標準品A450值繪制標準曲線，根據(jù)樣品的A450值在坐標上找出對應的濃度，根據(jù)稀釋倍數(shù)計算標本中IL-1β和sE-selectin實際含量。

四、統(tǒng)計學處理

結(jié) 果

一、一般情況

5例SAP在病情穩(wěn)定后行手術(shù)治療，1例為胰腺假性囊腫，1例為胰腺膿腫，3例為膽囊結(jié)石。除1例患者死于多器官功能衰竭外，其他患者均治愈出院。MAP和SAP兩組患者平均年齡及性別比均無統(tǒng)計學差異(P>0.05 )。住院天數(shù)、APACHEⅡ評分相差顯著(P<0.05)。

二、血清IL-1β含量的變化

對照組血清IL-1β濃度為(18.71±2.43)ng/L。MAP組患者入院后1、3、7 d的IL-1β濃度分別為(61.18±7.47)ng/L、(33.03±5.85)ng/L、(20.73±4.07)ng/L，1、3 d顯著高于對照組(P<0.05)，7 d與對照組無顯著差異。SAP組患者入院后1、3、7、14 d的血清IL-1β濃度分別為(86.91±13.32)ng/L、(81.35±12.71)ng/L、(64.93±5.99)ng/L、(21.40±49.13)ng/L，峰值出現(xiàn)在入院后1 d，1、3、7 d顯著高于對照組和MAP組(P<0.05 ),14 d與對照組無顯著差異。

三、血清sE-selectin濃度的變化

對照組血清sE-selectin濃度為(10.69±2.51)ng/ml。MAP組患者入院后1、3、7 d的sE-selectin濃度分別為(41.60±6.85)ng/ml、(14.90±3.51)ng/ml、(9.85±2.88)ng/ml，1、3 d顯著高于對照組(P<0.05)，7 d與對照組無顯著差異。SAP組患者入院后1、3、7、14 d的血清sE-selectin濃度分別為(84.73±15.37)ng/ml、(95.65±13.06)ng/ml、(39.41±3.73)ng/ml、(12.25±2.29)ng/ml，峰值出現(xiàn)在入院后3 d，1、3、7 d顯著高于對照組和MAP組(P<0.05 )，14 d與對照組無顯著差異。

四、血清IL-1β和sE-selectin濃度的關(guān)系

AP患者僅在入院后第1天，血清的IL-1β含量和sE-selectin含量存在正相關(guān)關(guān)系(r=0.851，P<0.01,圖1)。

討 論

近年來研究認為，TNF及IL-1β在MAP向SAP演進過程中具有重要作用。它們能夠?qū)е缕渌毎蜃蛹案鞣N內(nèi)源性的化學介質(zhì)的產(chǎn)生[3]，其中IL-1β能夠引起白細胞聚集、上調(diào)黏附分子表達、激發(fā)巨噬細胞產(chǎn)生細胞因子及增加毛細血管通透性[4]。

圖1 AP患者血清IL-1β與sE-selectin關(guān)系

Tanaka等[5]報道，急性壞死性胰腺炎(ANP)大鼠并發(fā)的多器官功能衰竭至少部分由IL-1β激活引起。應用IL-1β拮抗劑，盡管不能減輕胰腺的病變程度，但可降低病死率，增加尿量，減少粒細胞的肺內(nèi)浸潤。Norman等[6]制備IL-1β受體基因缺失小鼠的AP模型，發(fā)現(xiàn)胰腺損傷的發(fā)展和炎癥反應均需通過IL-1β受體激活的介導。本試驗結(jié)果顯示，血清IL-1β水平與AP病情的輕重程度相關(guān)，提示檢測血清IL-1β濃度有助于評價AP的嚴重程度。

sE-selectin是與膜結(jié)合的E-selectin水解后的產(chǎn)物，可作為一個特異性的內(nèi)皮系統(tǒng)激活或損傷標志物[7]。Lundberg等[8]研究發(fā)現(xiàn)， E-selectin與白細胞在肺部的聚集相關(guān)，肺部損傷可能是由E-selectin介導的。Wereszczynska-Siemiatkowska等[9]觀察28例SAP和28例MAP患者入院后第1、3、5、10天血漿sE-selectin濃度，結(jié)果顯示兩組血漿sE-selectin濃度都高于非胰腺炎腹痛組，且SAP患者sE-selectin濃度升高更為顯著。而且MAP患者血漿sE-selectin濃度下降較快，而SAP患者則維持在較高水平。Ida等[10]報道，27例AP患者血漿sE-selectin水平在入院時均升高。但Pezzilli等[11]報道SAP患者血清E-selectin濃度與健康個體相比較無顯著意義。本試驗結(jié)果顯示，AP患者血清sE-selectin水平升高，且與病情的輕重具有一定關(guān)系，因此，檢測血清sE-selectin亦可以作為評價AP嚴重程度的一個指標。而IL-1β濃度升高先于sE-selectin的原因是IL-1β作用于血管內(nèi)皮細胞，使其過度表達E-selectin，后者水解成sE-selectin，再從血管內(nèi)皮細胞脫落入血所致。

[1] Bhatia M,Wong FL,Cao Y,et al.Pathophysiology of acute pancreatitis.Pancreatology,2005,5:132-144.

[2] 中華醫(yī)學會消化病學分會胰腺病學組.中國急性胰腺炎診治指南(草案).胰腺病學,2004, 4:35-38.

[3] Sawa H,Ueda T,Takeyama Y,et al.Role of toll-like receptor 4 in the pathophysiology of severe acute pancreatitis in mice.Surg Today,2007,37:867-873.

[4] Fink G,Yang J,Carter G,et al.Acute pancreatitis-induced enzyme release and necrosis are attenuated by IL-1 antagonism through an indirect mechanism.J Surg Res,1997,67:94-97.

[5] Tanaka N,Murata A,Uda K,et al.Interleukin-1 receptor antagonist modifies the changes in vital organs induced by acute necrotizing pancreatitis in a rat experimental model.Crit Care Med,1995,23:901-908.

[6] Norman J,Franz M,Messina J,et al.Interleukin-1 receptor antagonist decreaes severity of experimental acute pancreatitis．Surgery，1995,117:648-655.

[7] Bhatia M,Neoptolemos JP,Slavin J.Inflammatory mediators as therapeutic targets in acute pancreatitis.Curr Opin Investig Drugs,2001,2:496-501.

[8] Lundberg AH,Granger DN,Russell J,et al.Quantitative measurement of P-and E-selectin adhesion molecules in acute pancreatitis:correlation with distant organ injury.Ann Surg,2000,231:213-222.

[9] Wereszczynska-Siemiatkowska U,Dabrowski A,Siemiatkowski A,et al.Serum profiles of E-selectin,interleukin-10,and interleukin-6 and oxidative stress parameters in patients with acute pancreatitis and nonpancreatic acute abdominal pain.Pancreas,2003,26:144-152.

[10] Ida S,Fujimura Y,Hirota M,et al.Significance of endothelial molecular markers in the evaluation of the severity of acute pancreatitis.Surg Today,2009,39:314-319.

[11] Pezzilli R,Corsi M,Barassi A,et al.Serum adhesion molecules in acute pancreatitis:time course and early assessment of disease severity.Pancreas,2008,37:36-41.

2010-01-19)

(本文編輯：屠振興)

DynamicchangesandsignificanceofserumIL-1βandsE-selectininpatientswithacutepancreatitis

HUDuan-min,ZHOUChun-hua,WANGShao-feng.

DepartmentofGastroenterology,SecondAffiliatedHospital,SuzhowUniversity,Suzhou215004,China

WANGShao-feng,Email:sfwang68@yahoo.com.cn

ObjectiveTo investigate the dynamic changes and relationship between the serum levels of IL-1β and sE-selectin in acute pancreatitis (AP) patients, and to study the predicative value for severity of AP.MethodsForty one patients with AP were divided into severe acute pancreatitis (SAP,19 cases) group and mild acute pancreatitis (MAP, 22 cases) group．Their serum were collected at the 1st, 3rd, 7th, and 14th day after admission and the serum concentrations of IL-1β and sE-selectin were detected by ELISA. Another 20 healthy volunteers were selected as controls.ResultsThe serum concentration of IL-1β in control group was (18.71±2.43)ng/L, while they were (61.18±7.47)ng/L, (33.03±5.85)ng/L, (20.73±4.07)ng/L in MAP group at the 1st, 3rd, 7th day; and they were (86.91±13.32)ng/L, (81.35±12.71)ng/L, (64.93±5.99)ng/L, (21.40±49.13)ng/L at the 1st, 3rd, 7th and 14th day in SAP group. The serum concentration of IL-1β of patients with SAP were markedly higher than those with MAP and normal controls on the 1st, 3rd, 7th day (P<0.05) and they decreased almost to normal on the 14th day. The serum concentration of sE-selectin was (10.69±2.51)ng/ml, while they were (41.60±6.85)ng/ml, (14.90±3.51)ng/ml, (9.85±2.88)ng/ml in MAP group at the 1st, 3rd, 7th day; and they were (84.73±15.37)ng/ml, (95.65±13.06)ng/ml, (39.41±3.73)ng/ml, (12.25±2.29)ng/ml on the 1st, 3rd, 7th and 14th day. The serum concentration of sE-selectin of patients with SAP were significantly higher than those with MAP and normal controls on the 1st, 3rd, 7th day (P<0.05) and there was no significant difference between SAP and control group on the 14th day. There was a positive correlation between the serum level of IL-1β and sE-selectin in AP on the 1st day after admission (r=0.851,P<0.01).ConclusionsThe serum concentrations of IL-1β and sE-selectin are useful for AP severity predication.

Pancreatitis; IL-1β; E-selectin

10.3760/cma.j.issn.1674-1935.2010.06.002

215004 江蘇蘇州，蘇州大學附屬第二醫(yī)院消化科

王少峰,Email:sfwang68@yahoo.com.cn