高迁移率族蛋白1在急性坏死性胰腺炎伴器官功能损害中的作用及其抗体的保护作用  

Role of HMGBI in organ injury during acute necrotizing pancreatitis and protective effect of HMGB1monoclonal antibody

作　　者：夏敏[1] 张婷[2] 郭继中[1] 陈卫昌[3] 

机构地区：[1]南京医科大学附属无锡人民医院消化科,无锡214023 [2]江苏省中医院消化科 [3]苏州大学附属第一医院消化科

出　　处：《中华胰腺病杂志》2013年第1期32-35,共4页Chinese Journal of Pancreatology

摘　　要：目的 探讨高迁移率族蛋白1（HMGBI）在急性坏死性胰腺炎（ANP）伴器官功能受损发生过程中的作用。方法雄性ICR小鼠按数字表法随机分为对照组、ANP组和HMGBl单抗处理组（抗体组）。采用20％L-精氨酸腹腔注射制备小鼠ANP模型，抗体组于建模成功后即刻给予腹腔内注射HMGBl单抗200μg。制模后12、24、48h分批处死小鼠，取血检测血清淀粉酶活性及肝、肾功能指标，ELASA法检测血HMGBI水平，取胰腺及肝脏组织行常规病理检查并评分，实时荧光定量PCR法检测胰腺和肝脏组织HMGBlmRNA表达。结果对照组、ANP组、抗体组12h时的血清HMGBl水平分别为（9．09±1．03）、（25．04±4．30）、（16．84±4．27）μg／L；胰腺病理评分为（1．50±0．55）、（4．33±0．52）、（3．03±0．32）分；胰腺组织HMGBl mRNA表达量为0，48±0．18、7．53±2．71、3．26±2．33；肝脏组织HMGBl mRNA表达量为-1．23±0．37、0．15±0．65、-1．27±0．72。ANP组的上述指标均显著高于对照组（P值均〈0．05），而抗体组均显著低于ANP组（P值均〈0．05）。造模后24h血清HMGBI水平与胰腺病理评分呈线性正柏关（r=0．768，P〈0．05）。此外，各组血清淀粉酶、谷草转氨酶、谷丙转氨酶、乳酸脱氢酶、尿素氮、肌酐水平的变化趋势同血清HMGBI的变化，血清HMGBl水平与肌酐、尿素氮、谷丙转氨酶水平呈线性正相关（r值分别为0．824、0．719、0．590，P值均〈0．05）。结论HMGBl可能是ANP小鼠体内炎症反应卡和器官功能损害的关键因子，外源性给子其抗体可减轻ANP时胰腺及其他器官功能受损程度。Objective To investigate the role of HMGBI in the pathogenesis of organ injury of acute necrotizing panereatitis （ANP）. Methods Male ICR mice were randomly allocated into control group, ANP group and HMGB1 monoclnnal antibody group. ANP model was induced by intraperitoneal injection of 20% L-arginine. Mice in HMGBI monoelonal antibody group were given intraperitoneal injection of 200μg of HMGB1 rnonoclonal antibody immediately after the induction of the ANP model. All the mice were sacrificed at 12, 24, and 48 h after ANP induction. Serum level of amylase and liver, renal function were determined, level of serum HMGBI was measured by using enzyme-linked immunosorbent assay ,and then the pathologic changes of pancreas and liver were routinely observed and scored. The HMGB1 mRNA levels in the liver and pancreas were studied by real time fluorescence quantitative PCR. Results The serum levels of HMGB1 at 12 h in eontrol group, ANP group and HMGB I monoelonal antibody group were （9.09 ± 1.03）, （25.04 ± 4.30）,（ 16.84 ± 4.27 ）μg/L; and pathological scores of pancreatic tissue were （ 1.50 ± 0.55 ）, （4.33 ± 0.52 ） , （3.03 ±0.32） points; and HMGBI mRNA expressions in pancreas were 0.48 ±0.18, 7.53 ±2.71 , 3.26 ± 2.33 ; HMGB1 mRNA expressions in liver were - 1.23 ± 0.37, 0. 15 ± 0.65, - 1.27 ± 0.72. The corresponding values in ANP group were significantly higher than those in control group （ P 〈 0.05 ）. While the corresponding values in HMGB1 monoelonal antibody group were significantly lower than those in ANP group （P 〈 0.05 ）. There was a positive linear relationship between serum HMGB1 level and pancreatic pathological scores 24 h after ANP induction （ r = 0.768, P 〈 0.05 ）. In addition, the serum levels of AMY, AST, ALT, LDH, BUN, Cr showed a similar trend as that of serum level of HMGB1, and the serum level of HMGB1 was positively associated with serum levels of Cr, BUN and ALT （ r =0. 824, 0. 719, 0. 590, P 〈0.05 ）. Conclusions HMGB1 may be a key facto

关 键 词：胰腺炎 急性坏死性 高迁移率族蛋白质类 抗体 单克隆 

分 类 号：R57[医药卫生—消化系统]