高迁移率族蛋白B1在重症急性胰腺炎肠屏障损害中的作用  

Role of high mobility group box-1 protein in gut mucosal barrier dysfunction during severe acute pancreatitis in rats

作　　者：栾正刚[1] 张成[2] 葛春林[2] 马晓春[1] 郭仁宣[2] 

机构地区：[1]中国医科大学附属第一医院重症医学科,辽宁省沈阳市110001 [2]中国医科大学附属第一医院普外二科,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2007年第30期3173-3177,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨高迁移率族蛋白B1在重症急性胰腺炎(SAP)肠屏障损害中的作用及其机制.方法:采用逆行胆胰管注射50 g/L牛磺胆酸钠制备SAP大鼠模型.将56只Wistar大鼠随机分为正常对照组(Control组),SAP 3h,6h,12h,24h,48h 5个亚组,二硫代氨基甲酸吡咯烷处理组(PDTC组),每组8只.PDTC组于建模后24h取材.测定血浆内毒素(LPs)、二胺氧化酶(DAO)水平,用逆转录-聚合酶链反应(RT-PCR)方法检测肠组织高迁移率族蛋白B1(HMGB1)mRNA表达,用Western blot法检测肠组织HMGB1水平.结果:与对照组比较,SAP 6h组大鼠肠组织HMGB 1 mRNA表达显著增高(0.41±0.06 vs 0.26±0.03,P<0.01),12h呈现进一步升高趋势,24h达峰值(0.62±0.06),并持续至48h.PDTC干预可显著降低肠组织HMGB1 mRNA表达(0.35±0.06 vs 0.62±0.06,P<0.01).PDTC组较SAP 24h组肠组织HMGB1 mRNA表达,血浆LPS和DAO显著下降(HMGB1 mRNA表达:0.35±0.06 vs 0.62±0.06,P<0.01;LPS:0.433±0.120 KEU/L vs 0.852±0.232 KEU/L,P<0.01;DAO:0.65±0.12 kU/L vs 1.36±0.22 kU/L,P<0.01).结论:SAP时,肠组织内HMGB1表达上调;PDTC可以明显抑制SAP时肠组织内HMGB1表达.AIM： To investigate the role of high mobility group box-1 protein （HMGB1） in gut mucosal barrier dysfunction during severe acute pancreatitis （SAP） in mice, and the mechanisms involved. METHODS： A rat model of SAP was established by retrograde injection of 50 g/L sodium taurocholate into the choledochopancreatic duct. Fifty-six healthy male Wistar rats were divided randomly into three groups： control, SAP （3, 6, 12, 24 and 48 hours subgroups）, and pyrrolidine dithiocarbamate （PDTC）. Plasma lipopolysaccharide （LPS） and blood diamine oxidase （DAO） levels were determined. The expression of HMGB1 mRNA in the intestinal mucosa was de-tected by reverse-transcription polymerase chain reaction （RT-PCR）, and the activity of HMGB1 was determined by Western blotting. RESULTS： Compared with the normal control group, HMGB1 mRNA level markedly increased in intestinal mucosa 6 hours after SAP （0.41 ± 0.06 vs 0.26 ± 0.03, P 〈 0.01）, peaked at 24 hours （0.62 ± 0.06）, and remained relatively high up to 48 hours. Meanwhile, HMGB1 mRNA expression was significantly inhibited by PDTC in the intestine 24 hours after SAP （0.35 ± 0.06 vs 0.62 ± 0.06, P 〈 0.01）. PDTC alleviated the blood level of endotoxin and DAO 24 hours after SAP （LPS, 0.433 ± 0.120 KEU/L vs 0.852 ± 0.232 KEU/L, P 〈 0.01; DAO, 0.65 ± 0.12 kU/L vs 1.36 ± 0.22 kU/L, P 〈 0.01）. CONCLUSION： The expression of HMGB1 mRNA increases in the intestine during SAP. PDTC markedly inhibits HMGB1 mRNA gene expression.

关 键 词：重症急性胰腺炎 肠黏膜屏障 二硫代氨基甲酸吡咯烷 高迁移率族蛋白B1 逆转录-聚合酶链式反应:免疫印迹 

分 类 号：R576[医药卫生—消化系统]