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溃疡性结肠炎患者血清可溶性细胞间粘附分子-1表达的研究

2014-02-20施颖琦仇建伟葛振明王亚民钱俊波

交通医学 2014年1期
关键词:溃疡性结肠炎程度

施颖琦,陆 飞,仇建伟,葛振明,王亚民,钱俊波

(南通市第一人民医院消化内科,江苏226001)

溃疡性结肠炎患者血清可溶性细胞间粘附分子-1表达的研究

施颖琦*,陆 飞,仇建伟,葛振明,王亚民,钱俊波

(南通市第一人民医院消化内科,江苏226001)

目的:检测溃疡性结肠炎患者血清可溶性细胞间粘附分子-1(sICAM-1)水平的变化,探讨sICAM-1对溃疡性结肠炎疾病进展程度的作用。方法:溃疡性结肠炎32例、健康体检者20例为研究对象,采用ELISA法检测血清SICAM-1水平,分析其与临床分型、病变范围、疾病严重程度、肠外表现与CRP、ESR的关系。结果:(1)sICAM-1水平:溃疡性结肠炎组305.34±73.33ng/mL,对照组189.72±56.46ng/mL,两组比较差异有统计学意义(P<0.05)。(2)sICAM-1与临床分型关系:初发型15例sICAM-1 283.45±90.02ng/mL,慢性反复发作型17例sICAM-1为292.36± 78.91ng/mL,两者比较差异无统计学意义(P>0.05)。(3)sICAM-1与病变范围关系:E1(直肠)14例,E2(左半结肠)12例,E3(广泛结肠)6例,其sICAM-1分别为264.22±89.43ng/mL、275.36±97.91ng/mL、336.45±73.02ng/mL,E1组与E2组比较差异无统计学意义(P>0.05),E3组与E1、E2组比较差异有统计学意义(P<0.05)。(4)sICAM-1与疾病程度关系:轻度10例,中度16例,重度6例,其sICAM-1分别264.22±67.27ng/mL、302.36±54.34ng/mL、336.45±73.02ng/mL,3组间比较差异有统计学意义(P<0.05)。(5)sICAM-1肠外表现:肠外表现11例,sICAM-1为312.23±89.02ng/mL。无肠外表现21例sICAM-1为295.11±65.02ng/mL,两者比较差异无统计学意义(P>0.05)。(6)sICAM-1水平与CRP、ESR的关系:sICAM-1与CRP成正相关,r值为0.561(P<0.05);sICAM-1与ERS成正相关,r值为0.478(P<0.05)。结论:sICAM-1水平与UC病变范围及严重程度相关,可作为评估UC炎症程度指标之一。

溃疡性结肠炎;血清细胞间粘附分子-1;酶联免疫吸附试验

溃疡性结肠炎(ulcerative colitis,UC)是一种病因未明、主要累及结肠粘膜的自身免疫性疾病,细胞因子及粘附分子在UC的发病中起重要作用。细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)属粘附分子中的免疫球蛋白超家族,主要表达于内皮细胞。我院消化内科2010年12月—2013 年3月收治溃疡性结肠炎患者32例,通过测定溃疡性结肠炎患者血清中可溶性ICAM-l(sICAM-l)水平,探讨sICAM-1与UC疾病进展程度之间关系以

及对UC的预后判断的评估价值,报告如下。

1 资料与方法

1.1 一般资料 溃疡性结肠炎患者32例,其中男18例,女14例,年龄21~58岁,中位年龄39岁。对照组20例,其中男10例,女10例,年龄25~55岁,中位年龄35岁,均为健康体检者。两组间性别、年龄等一般资料均具有可比性(P>0.05)。

1.2 方法 (1)人sICAM-1ELISA试剂盒(武汉博士德生物工程有限公司)。就诊时空腹抽静脉血2mL,血标本5 000 r/min、15 min离心分离血清,冻存于-80℃冰箱中备检。ELISA法检测血清sICAM-

1。操作步骤按试剂盒说明书进行。CRP由本院检验科检测。

1.3 统计学处理 采用SPSS 13.0统计软件进行统计学分析。计量数据均以均数±标准差(±s)表示,采用成组设计两样本均数比较的t检验,直线相关分析相关性;P<0.05表示差异有统计学意义。

2 结 果

2.1 两组sICAM-1水平比较及临床分型关系 (1)溃疡性结肠炎组sICAM-1为(305.34±73.33)ng/mL,对照组sICAM-1为(189.72±56.46)ng/mL,两组比较差异有统计学意义(P<0.05)。(2)与临床分型关系:32例 UC中初发型 15例 sICAM-1为(283.45± 90.02)ng/mL,慢性反复发作型17例sICAM-1为(292.36±78.91)ng/mL,两者比较差异无统计学意义(P>0.05)。

2.2 sICAM-1与病变范围分类及疾病活动严重程度关系 32例UC中E1(直肠)14例,E2(左半结肠)12例,E3(广泛结肠)6例,其E1组与E2组比较差异无统计学意义(P>0.05),E3组与E1、E2组比较差异有统计学差异意义(P<0.05)。根据改良Truelove 和Witts严重程度分类标准评分[1],32例UC中轻度10例,中度16例,重度6例,3组间比较差异有统计学意义(P<0.05),见表1。

表1 sICAM-1与病变范围及疾病活动严重程度分类关系

2.3 sICAM-1肠外表现及与 CRP、ESR的关系(1)UC 32例中存在肠外表现11例,sICAM-1为(312.23±89.02)ng/mL。不存在肠外表现 21例。sICAM-1为(295.11±65.02)ng/mL,两者比较差异无统计学意义(P>0.05)。(2)sICAM-1水平与CRP、ESR的关系:sICAM-1与CRP成正相关,r值为0.561(P<0.05);sICAM-1与ERS成正相关,r值为0.478(P<0.05)。

3 讨 论

溃疡性结肠炎(UC),是一类以肠道炎症为主要表现的慢性复发性肠道自身免疫性疾病。治疗颇为棘手,疾病常易复发,其发病机制仍未完全阐明且治疗手段有限。病程中需反复肠镜查看肠道病变范围、严重程度。操作中患者痛苦性增加、病情评估易受操作医师主观因素影响,现有UC的血清学检查有限。因此寻找新的、有效的血清学指标评估病情已成为目前研究的热点和方向。

粘附因子在肠道的炎症发生中起重要作用[2-3]。淋巴细胞在从血管内迁移到炎症部位的过程中,首先同选择素P结合。然后再通过和内皮细胞间粘附分子ICAM-1牢固结合,最后同血管粘附因子(vascular cell adhesion molecule-1,VCAM-1)及粘膜血管 定 居 因 子 (mucosal addressin cell adhesion molecule-1,MadCAM-1)相结合完成迁移过程,其中淋巴细胞与ICAM-1间的结合起到决定性作用。ICAM-1属粘附分子中的免疫球蛋白超家族,主要表达于内皮细胞,主要通过和淋巴细胞功能相关抗原-1结合介导淋巴细胞浸润和迁移[4]参与炎症和免疫反应。相关证据表明,ICAM-1在炎症性肠病的发生发展过程中具有重要作用。Videm V等[5]发现可溶性sICAM-1被认为是血管内皮细胞激活的重要标志。ICAM-1能够促进淋巴细胞与血管内皮细胞的粘附和淋巴细胞向炎症部位的迁移,共同介导免疫效应细胞与多种细胞及免疫细胞间的相互作用,在机体免疫系统中起重要作用[6-7]。

在IBD小鼠模型中给予ICAM-1抗体治疗后小鼠肠粘膜炎症减轻、淋巴细胞浸润减少、髓过氧化物酶活性减轻[8-9];ICAM-1重要组成为α4黏合素,针对该粘合素的单克隆抗体如Natalizumab,已开始应用于临床,其前期临床试验也获得初步疗效[10-11]。提示ICAM-1与肠道炎症关系密切,sICAM-1水平检测对UC疗效评估指导意义。Vainer B等[12]发现ICAM-1在正常人粘膜中的表达较低,而在IBD患者中明显升高,且与疾病活动指数呈正相关。该结果与本实验中UC患者sICAM-1水平明显高于对照组,sICAM-1与结肠病变范围、疾病活动严重程度,根据改良Truelove和Witts严重程度分类标准评分结果一致。

sICAM-1水平与CRP、ESR成正相关,表明sICAM-1与UC炎症反应程度有关,因此sICAM-1可作为评估UC炎症程度指标之一。但对于是否存在肠外表现,本实验中sICAM-1水平两组比较差异无统计学意义,有关该现象还需更多临床资料进一步验证。

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[2]Yang H.Analysis of ICAM-1 gene polymorphism in immunologic subsets of inflammatory bowel disease[J].Exp Clin Immunogenet,1997,14(3):214-225.

[3]丁炎波,邹开芳.趋化因子及其受体与炎症性肠病[J].国际消化病杂志,2007,27(1):44-46.

[4]Rothlein R,Dustin ML,Marlin SD,et al.A human intercellular adhesion molecule (ICAM-1)distinct from LFA-1[J]. Journal of Immunology,1986,137(4):1270-1274.

[5]Videm V,Albrigtsen M.Soluble ICAM-1 and VCAM-1 as markers of endothelial activation [J].Scand J Immunol, 2008,67(5):523-531.

[6]Yang L,Froio RM,Sciuto TE,et al.ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alphaactivated vascular endothelium under flow[J].Blood,2005, 106(2):584-592.

[7]Scaldaferri F,Sans M,Vetrano S,etal.The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease[J].Eur J Immunol,2009,39(1):290-300.

[8]Picarella D,Hurlbut P,Rottman J,et al.Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1)reduce inflammation in the colon of scid mice reconstituted with CD45RBhigh CD4+ T cells[J].J Immunol,1997,158(5):2099-2106.

[9]Taniguchi T,Tsukada H,Nakamura H,et al.Effects of the anti-ICAM-1 monoclonal antibody on dextran Sodium sulphate-induced colitis in rats[J].J Gastroenterol Hepatol, 1998,13(9):945-949.

[10]Sandborn WJ,Colombel JF,Enns R,et al.Natalizumab induction andmaintenance therapy for Crohn's disease[J].N Engl JMed,2005,353(18):1912-1925.

[11]Gordon FH,Hamilton MI,Donoghue S,et al.A pilot study of treatment of active ulcerative colitis with natalizumab,a humanized monoclonal antibody to alpha-4 integrin[J].Aliment Pharmacol Ther,2002,16(4):699-705.

[12]Vainer B,Nielsen OH.Changed colonic profile of P-selectin,platelet-endothelial cell adhesion molecule-1 (PECAM-1),intercellular adhesionmolecule-1(ICAM-1),ICAM-2,and ICAM-3 in inflammatory bowel disease[J].Clin Exp Immunol,2000,121(2):242-247.

Study of serum intercellular adhesion molecule-1 in patientsw ith ulcerative colitis

SHIYingqi,LU Fei,QIU Jianwei,GE Zhengming,WANG Yamin,QIAN Junbo
(Departmentof Gastroenterology,Nantong First People's Hospital,Jiangsu 226001)

Objective:To determine the serum levels of intercellular adhesionmolecule-1(sICAM-1)in patientswith ulcerative colitis and to investigate the contributions of sICAM-1 in pathogenesis of UC.Methods:The serum ICAM-1 concentrationswere determined by enzyme-linked immunosorbent assay in 32 patients with UC and 20 healthy controls at the time of admission.The relationships between the sICAM-1 levels and the clinical type,the extent,the severity,Extraintestinal complications,CRP and ESR were analized.Results:(1)the levels of sICAM-1:Themean value of sICAM-1 level in the UC group(305.34±73.33ng/mL)was significantly higher than in the health group(189.72±56.46ng/mL)(P<0.05).(2)the relationgships between sICAM-1 and clinical classification:There were no remarkable relationships between the levels of sICAM-1 in 15 patients of the first attack group(283.45±90.02ng/mL)and 17 patients of the recurrent attack group (292.36±78.91ng/mL)(P>0.05).(3)the relationgships between sICAM-1 and the extent of disease:14 patients in E1(the rectal group),12 patients in E2(the sigmoid group),6 patients in E3(the extensive colonic group).There were no remarkable relationships between sICAM-1 in the E1 group (264.22±89.43ng/mL)and the E2 group(275.36±97.91ng/mL)(P> 0.05),but the levels of sICAM-1 in the E3 (336.45±73.02ng/mL)group was significantly higher than in the E1group and the E2 group(P<0.05).(4)the relationgships between sICAM-1 and different degrees of severity of disease:10 patients in the light group (264.22±67.27ng/mL),16patients in the moderate group (302.36±54.34ng/mL),6 patients in the severe group(336.45±73.02ng/mL),the levels of sICAM-1 between the three groupswith differernt degrees of severity of UCwere significantly different(P<0.05).(5)the relationgships between sICAM-1 and Extraintestinal complications:11 patientswith extraintestinal complications(312.23±89.02ng/mL),21 patients without extraintestinal complications(295.11±65.02ng/mL), there were no remarkable relationships between sICAM-1 and Extraintestinal complications(P>0.05).(6)the relationgships between sICAM-1 and CRP and ESR:sICAM-1 was positively correlated with CRP(r=0.561,P<0.05))and ESR(r=0.478,

ulcerative colitis;serum intercellular adhesion molecule-1(sICAM-1);enzyme-linked immunosorbent assay(ELISA)

R574.62

A

施颖琦,女,汉族,江苏南通人,生于1985年7月,硕士研究生,住院医师。研究方向:消化病学。E-mial:yingqishi7@163.com

2014-01-12

1006-2440(2014)01-0027-03

P<0.05).Conclusions:sICAM-1 levels were correlated with the extent and the severity of UC.The measurement of sICAM-1may be valuablemarkers to evaluate the severity for patientswith ulcerative colitis.

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