高迁移率族蛋白-1在脓毒症所致多器官功能损害中的作用  

The potential role of high mobility group-1 protein in the pathogenesis of seps

作　　者：张立天 姚咏明 陆家齐 董宁 于燕 鄢小建 方文慧 盛志勇 

机构地区：[1]解放军第三○四医院创伤外科中心,北京100037

出　　处：《中华外科杂志》2003年第4期303-306,共4页Chinese Journal of Surgery

基　　金：国家重点基础研究发展规划资助项目(G19990 5 42 0 3);国家杰出青年科学基金 ( 30 12 5 0 2 0 );军队十五医药卫生科研基金资助项目 ( 0 1MA2 0 7)

摘　　要：目的　观察高迁移率族蛋白 1(HMG 1)在脓毒症中的变化规律及其与多器官功能损害的关系。　方法　采用大鼠盲肠结扎穿孔 (CLP)造成脓毒症模型。动物分为正常对照组 ( 10只 )、假手术组 ( 10只 )、盲肠结扎穿孔组 ( 6 0只 )及正丁酸钠治疗组 ( 2 0只 )。留取组织和血标本分别检测HMG 1mRNA表达及器官功能指标。另设实验观察正丁酸钠对脓毒症大鼠的治疗效果 ( 5 7只 )。结果　CLP术后 6～ 72h肝、肺、肾及小肠组织HMG 1mRNA表达均显著增强 (P <0 0 5或P <0 0 1)。正丁酸钠处理可显著降低CLP术后 12及 2 4h动物各组织HMG 1mRNA表达 ,12h血清丙氨酸转胺酶、肌酐水平比未治疗组显著降低 (P <0 0 1) ,2 4h肺组织髓过氧化物酶活性亦明显下降 (P <0 0 1)。早期给予正丁酸钠治疗 ,大鼠 1～ 6d存活率显著高于未治疗组 (P <0 0 5或P <0 0 1)。　结论　HMG 1在诱导脓毒症动物过度炎症反应与多器官功能损害中具有重要作用。Objective To investigate the potential role of high mobility group-1 protein (HMG-1) in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome in rats. Methods Using a sepsis model by cecal ligation and puncture (CLP), 80 male Wistar rats were randomly divided into four groups: normal control (n=10), sham operation (n=10), CLP (subdivided into 2,6,12,24,48,72 h post-CLP , n=60), and sodium butyrate treatment (subdivided into 12,24 h post-CLP, n=20). At serial time points in each group, animals were sacrificed, and blood as well as tissue samples from the liver, lung, kidney and small intestine were harvested to measure organ function parameters and HMG-1 mRNA expression by the reverse transcription polymerase chain reaction (RT-PCR) taking GAPDH as an internal standard. Also, additional experiments were performed to observe the effect of treatment with sodium butyrate on survival rate in septic rats (n=57). Results HMG-1 mRNA levels significantly increased in various tissues during 6～72 h after CLP ( P<0.05 or 0.01), and were markedly inhibited by sodium butyrate at 12 h and 24 h( P<0.05 or 0.01). Early treatment with sodium butyrate also could markedly reduce serum alanine aminotransferase, creatinine levels at 12 h post-CLP and pulmonary myeloperoxidase activities at 24 h. Furthermore, treatment with sodium butyrate could significantly improve the 1- to 6-day survival rates in animals subjected to CLP ( P<0.05 or 0.01). Conclusions HMG-1 might play an important role in the development of excessive inflammatory response and subsequent multiple organ dysfunction syndrome.

关 键 词：高迁移率族蛋白-1 脓毒症 多器官功能损害 多器官功能衰竭 正丁酸钠 

分 类 号：R631[医药卫生—外科学]