血清高迁移率族蛋白1与急性胰腺炎严重程度相关性研究

芦照青 任爱民 王红 张淑文 文艳 杜琨 黄光伟

·论著·

血清高迁移率族蛋白1与急性胰腺炎严重程度相关性研究

芦照青 任爱民 王红 张淑文 文艳 杜琨 黄光伟

目的观察急性胰腺炎(AP)患者血清高迁移率族蛋白1(high mobility group box chromosomal protein-1，HMGB1)的水平，探讨HMGB1水平与AP严重程度的相关性。方法收集62例患者入院即刻及入院后24、48 h血标本，应用ELISA方法检测血清HMGB1水平，并分析其与AP病情严重程度的相关性。以20例健康成年人作为对照组。结果62例AP患者入院即刻及入院后24、48 h血清HMGB1水平分别为(8.05±1.60)、(8.04±1.39)、(8.25±1.56)ng/ml，均显著高于对照组的(2.20±0.57)mg/ml(P值均<0.01)。其中重症急性胰腺炎(SAP)35例，轻症急性胰腺炎(MAP)27例。SAP组患者血清HMGB1水平分别为(7.99±1.69)、(8.12±1.40)、(8.13±1.34)ng/ml；MAP组患者为(8.12±1.52)、(7.92±1.40)、 (8.39±1.81)ng/ml。两组间差异无统计学意义。结论AP患者的血清HMGB1水平显著高于正常人群，但其与AP的严重程度无平行关系。

胰腺炎； 高迁移率族蛋白质类； 病例对照研究

材料和方法

一、临床资料

研究对象为2008年3月至2009年2月北京友谊医院收治的62例AP患者，其中男33例(53.2%),女29例(46.8%)，年龄(55±17)岁。均在发病后72 h内入院，发病至入院的平均间隔时间为(34±20)h。患者入院即刻及入院后24、48 h分别取血清样本，于-80℃冻存待检。

AP的诊断标准：患者存在明确的临床症状、体征及影像学表现，血淀粉酶至少高于正常上限的3倍。根据我国2007年发布的《重症急性胰腺炎诊治指南》[2]，将AP患者分为SAP及轻症急性胰腺炎(MAP)两组，MAP患者27例，SAP患者35例。排除标准：住院时间不足24 h；近1周有手术史；发病前1月内有严重感染；ERCP术后胰腺炎。入院后均给予抑酶、抑酸、抗感染等常规非手术治疗。

另选取健康成年人20例作为对照组，其中男12例(60%)，女8例(40%)，年龄(42±17)岁。

二、血清HMGB1水平测定

血清HMGB1水平应用ELISA方法测定，试剂盒购自美国ALD公司，按说明书操作。本法组内差异<5%，组间差异<10%，敏感度0.01 ng/ml。

三、统计方法

结 果

一、一般资料

MAP与SAP患者的性别比、病因、发病至入院间隔时间、基础疾病、复发病例等均无显著性差异。但SAP组患者年龄、APACHEⅡ评分、Ranson评分、Balthazar CT分级及并发症发生率均显著高于MAP组(P值均<0.01，表1)。

二、AP患者血清HMGB1水平

入院即刻及入院后24、48 h时AP患者血清HMGB1水平分别为(8.05±1.60)、(8.04±1.39)、(8.25±1.56)ng/ml，均较健康对照组的(2.20±0.57)ng/ml显著增高(P值均=0.000)。

其中SAP组患者血清HMGB1水平分别为(7.99±1.69)、(8.12±1.40)、(8.13±1.34)ng/ml；MAP组分别为(8.12±1.52)、(7.92±1.40)、(8.39±1.81)ng/ml。两组间差异无统计学意义(P=0.77、0.62、0.53)。

表1 两组AP患者的一般临床资料比较

注：与MAP组比较，aP<0.01

讨 论

HMGB1是一种存在于细胞核内的非组蛋白的核蛋白，具有晚期炎症因子作用[3]。在脓毒症及其他炎性疾病中血清HMGB1水平亦显著升高[4-9]。动物实验结果表明，急性坏死性胰腺炎(ANP)大鼠血清HMGB1水平在建模后12 h开始明显升高，至建模后48 h仍维持在高水平，且与大鼠胰腺组织HMGB1 mRNA表达水平呈平行关系[10-11]。应用HMGB1联合牛磺胆酸钠逆行注射大鼠胰管可明显增加胰腺坏死[12]，但临床数据与动物实验结果并不一致。Sundén-Cullberg等[13]报道，脓毒症患者血清HMGB1水平与感染的严重程度并无相关性，病死组患者血清HMGB1甚至显著性降低。van Zoelen等[10]结果与其一致。Angus等[11]报道，社区获得性肺炎患者血清HMGB1水平与有无脓毒症无相关性。Yasuda等[14]报道，SAP患者血清HMGB1水平较正常人明显增高，但其与APACHEⅡ评分、Ranson评分并无相关性，且发生脏器衰竭、感染或病死患者血清HMGB1水平较其他SAP患者并无显著增高，提示其与疾病的严重程度并不呈明显平行关系。沈美琴等[15]报道，SAP患者血清HMGB1水平明显高于MAP者，MAP者又明显高于健康对照组，提示HMGB1水平与AP严重程度相关。本研究显示，AP患者血清HMGB1水平较正常人显著增高，但SAP组与MAP组患者血清HMGB1水平无显著性差异，提示HMGB1水平与AP的严重程度并无平行关系。因此，HMGB1在AP中的作用究竟如何，是否具有临床意义，尚需更大规模的临床研究数据加以论证。

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2010-08-24)

(本文编辑：屠振兴)

Therelationshipbetweenserumhighmobilitygroupboxchromosomalprotein-1levelsandtheseverityofacutepqncreatitis

LUZhao-qing,RENAi-min,WANGHong,ZHANGShu-wen,WENYan,DUKun,HUANGGuang-wei.

DepartmentofEmergencyMedicine,BeijingFriednessHospital,CapitalMedicalUnivesity,Beijing100050,China

RENAi-min,Email:julie444@126.com

ObjectiveTo investigate the high mobility group box chromosomal protein-1 (HMGB1) levels in patients with acute pancreatitis (AP); and to study the relationship between the serum level of HMGB1 and the severity of AP.MethodsThe patients′ serum HMGB1 concentrations were determined right after admission, 24, 48 hour after admission. The levels of HMGB1 were measured by ELASA kit and its relationship with the severity of AP was analyzed. 20 healthy adults were treated as the control group.ResultsAt the time of admission, and 24, 48 hours after admission, the serum HMGB1 levels in AP patients were (8.05±1.60), (8.04±1.39), (8.25±1.56)ng/ml, respectively, which were significantly higher than that in the healthy control [(2.20±0.57)ng/ml,P<0.01]. There were 35 patients with severe acute pancreatitis (SAP) and 27 patients with mild acute pancreatitis (MAP). The HMBG1 levels in patients with SAP were (7.99±1.69),(8.12±1.40), (8.13±1.34)ng/ml, and they were (8.12±1.52), (7.92±1.40), (8.39±1.81)ng/ml in patients with MAP, and the difference between the two groups was not statistically significant.ConclusionsThe serum HMGB1 level in AP patients was significantly higher than that in healthy controls, but it was not related with the severity of AP.

Pancreatitis; High mobility group proteins; CaseK-control studies

目前认为，重症急性胰腺炎(SAP)的发病有多种炎症因子的参与。高迁移率族蛋白1(high mobility group box chromosomal protein-1，HMGB1)是在30年前发现的非组蛋白的核蛋白[1]。1999年首次发现其在脓毒症中具有晚期炎症介质作用。进一步动物实验显示，HMGB1在SAP的发生、发展中发挥重要作用。本研究观察AP患者血清HMGB1水平，探讨其与疾病严重程度是否存在相关性。

10.3760/cma.j.issn.1674-1935.2011.04.002

北京市中医局5151工程项目

100050 北京，首都医科大学附属北京友谊医院感染暨急救医学科

任爱民，Email: julie444@126.com