核因子-κB抑制剂对内毒素休克大鼠高迁移率族蛋白B1表达的影响及机制  

Effects of NF-kappaB inhibitor(pyrrolidine dithiocarbamate)on tissue mRNA expression of high mobility group box-1 protein in rats with endotoxic shock

作　　者：胥彩林[1] 姚咏明[1] 于燕[1] 王松柏[1] 

机构地区：[1]解放军第304医院全军烧伤研究所基础部,北京100037

出　　处：《感染．炎症．修复》2003年第3期153-156,共4页Infection Inflammation Repair

基　　金：国家重点基础研究发展规划项目(编号G1999054203);国家杰出青年科学基金(编号30125020);军队十五医药卫生科研基金(编号01MA207)资助课题

摘　　要：目的:观察核转录因子-κB(NF-κB)抑制剂——二硫氨基甲酸酞吡咯烷(PDTC)对内毒素休克大鼠高迁移率族蛋白 B1(HMGB1)mRNA 表达的影响及机制。方法:采用内毒素休克模型,47只大鼠随机分为正常对照组(n=8)、内毒素休克组(n=24)和 PDTC 拮抗组(n=15),留取肝、肺、肾组织检测 HMGB1 mRNA 表达及相应器官功能指标的变化。结果:内毒素攻击可导致动物肝、肺、肾组织 HMGB1 mRNA 表达广泛上调,分别于2～6h 显著增高(P<0.05),12h 呈现进一步升高趋势。PDTC 处理后12h,肝、肺、肾组织 HMGB1 mRNA 表达均显著下调,其中肾组织2～12h 趋于伤前范围;同时,血清丙氨酸转移酶、天冬氨酸转移酶、尿素氮、肌酐水平6h 明显降低(P<0.05),肺组织髓过氧化物酶活性各时相点均显著低于内毒素休克组(P<0.05)。结论:NF-κB抑制剂能显著抑制内毒素休克动物组织 HMGB1 mRNA 的表达,NF-κB信号转导通路参与了内毒素介导 HMGB1基因表达的调控过程,并与脓毒症时多器官功能损害密切相关。Objective:To investigate the effect of nuclear factor-kappaB(NF-κB)signal transcription pathway inhibitor-pyrrolidine dithioearbamate(PDTC)on tissue mRNA expression of high mobility group box-1 protein (HMGB1)in rats after endotoxie shock and its potential mechanism.Methods:Using an endotoxic shock model, 47 male Wistar rats were randomly divided into normal control group(n=8),endotoxic shock group(n=24), and PDTC treatment group(n=15).At serial time points,animals in each group were sacrificed,and tissue sam- ples from the liver,lungs and kidneys were harvested to determine HMGB1 mRNA expression and pulmonary my- eloperoxidase(MPO)activity.Also,blood samples were collected to determine the functional indices of major or- gans.Results:Compared to normal controls,HMGB1 mRNA levels were significantly increased in the liver,lungs and kidneys at 2-6h after endotoxin challenge,respectively(P<0.05),and the high values sustained up to 12 h. Meanwhile,serum ALT,AST,BUN,Cr levels as well as pulmonary MPO activity significantly elevated in ani- mals following endotoxic shock(P<0.05 or 0.01).Treatment with PDTC could markedly down-regulate HMGB1 mRNA expressions in various organs at 12h compared with endotoxic shock group(P<0.05 or 0.01). In addition,PDTC treatment could significantly reduce serum ALT,AST,BUN,as well as Cr levels at 6h(P< 0.05)and MPO activities at 2-12h.Conclusions:These data suggested that NF-κB signal transcription pathway might be involved in regulating mRNA expression of HMGB1 in rats after endotoxic shock.Early treatment with NF-κB inhibitor can down-regulate HMGB1 gene expression in vital organs and attenuate endotoxin-induced multi- ple organ dysfunction.

关 键 词：脓毒症 高迁移率族蛋白 B1 信号转导 核因子-ΚB 

分 类 号：R45[医药卫生—治疗学]