延迟的丙酮酸乙酯治疗对重症急性胰腺炎大鼠胰外脏器损伤的影响及其机制  

Effects and mechanism of delayed ethyl pyruvate therapy on distant organ injury in rats with severe acute pancreaUtis

作　　者：杨智勇[1] 凌燕[1] 陶京[1] 周峰[1] 熊炯炘[1] 吴河水[1] 王春友[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胰腺外科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2007年第24期2638-2642,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金;No.30600593~~

摘　　要：目的:探讨延迟的丙酮酸乙酯(EP)治疗对重症急性胰腺炎(SAP)大鼠血清高迁移率族蛋白1(HMGB1)水平和胰外脏器损伤的影响.方法:96只大鼠随机分为3组,假手术组(Sham组,n=32)、重症急性胰腺炎组(SAP组,n= 32)和丙酮酸乙酯延迟治疗组(EP组,n=32),采用胰胆管逆行灌注人工胆汁的方法复制大鼠SAP模型.EP组建模12,18,30h分别尾静脉注射1次EP溶液30 mg/kg.建模后24和48h处死动物取材,取血清检测HMGB1水平及肝肾功能生化指标,取肺组织用于肺损伤检测.结果:延迟的EP治疗能有效降低SAP大鼠血清HMGB1水平.EP组血清丙氨酸转氨酶(ALT, 446±91 IU/L vs 53±98 IU/L.P<0.01)、天冬氨酸转氨酶(AS T.667±103 IU/L vs 1368±271 IU/L,P<0.01)、尿素氮(BUN,38±4 mg/ dL vs 41±4 mg/dL,P=0.05)和肌酐(Cr,1.2±0.3 mg/dL vs 1.8±0.3 mg/dL,P<0.01)水平以及肺湿/干比(8.22±0.42 vs 9.76±0.45,P<0.01)和组织学评分(7.1±0.7 vs 8.4±1.1,P<0.01)均明显低于SAP组.结论:延迟的EP治疗通过下调血清HMGB1水平减轻SAP大鼠胰外脏器损伤.EP可能是SAP患者抗炎治疗和脏器功能保护的有效选择.AIM： To investigate the effects of delayed ethyl pyruvate （EP） delivery on distant organ injury and serum high mobility group box protein 1 （HMGB1） levels in rats with severe acute pancreatitis （SAP）. METHODS： The SAP animal model was induced by retrograde injection of artificial bile into the pancreatic duct in rats. Rats were randomly divided into three groups; sham, AHNP and delayed EP treatment （n = 32 in each group）. Rats in the delayed EP treatment group received EP （30 mg/kg） at 12, 18 and 30 hours after induction of SAP. Animals were sacrificed and samples were obtained at 24 and 48 hours after induction of SAP. Levels of serum HMGB1,aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） were measured. Lung wet- to-dry weight （W/D） ratio and histological score were calculated to evaluate lung injury. RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels and protected against liver, kidney and lung injury, with a re- duced lung W/D ratio （8.22 ± 0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological score （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 IU/L vs 1368 ± 271 IU/L, P 〈 0.01）, ALT （446 ± 91 IU/L vs 653 ± 98 IU/L, P 〈 0.01）, BUN （38 ± 4 mg/dL vs 41 ± 4 mg/dL, P 〉 0.05） and Cr （1.2 ± 0.3 mg/dL vs 1.8 ± 0.3 mg/dL, P 〈 0.01） levels. CONCLUSION： Delayed EP therapy protects against distant organ injury by reducing serum HMGB1 levels in rats with experimental SAP. EP appears to be an effective new therapeutic option against inflammatory responses and multiple organ dysfunction syndrome in SAP patients.

关 键 词：重症急性胰腺炎 高迁移率族蛋白1 丙酮 酸乙酯 多脏器功能不全 

分 类 号：R576[医药卫生—消化系统]