脓毒症大鼠肾组织高迁移率族蛋白-1对肿瘤坏死因子-α表达的影响  

THE EFFECT OF HIGH MOBILITY GROUP-1 PROTEIN ON TUMOR NECROSIS FACTOR-α EXPRESSION IN KIDNEY OF SEPTIC RATS

作　　者：姚咏明[1] 张立天[1] 陆家齐[1] 董宁[1] 鄢小建[1] 于燕[1] 方文慧[1] 盛志勇[1] 

机构地区：[1]解放军第304医院,北京100037

出　　处：《解放军医学杂志》2002年第9期757-759,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础发展规划项目 (编号G1 9990 542 0 3);国家杰出青年科学基金 (编号 30 1 2 50 2 0 );军队十五指令性课题 (编号 0 1L0 81 );军队十五医药卫生科研基金 (编号 0 1MA2 0 7)资助课题

摘　　要：采用大鼠盲肠结扎穿孔 (CLP)造成脓毒症模型 ,探讨脓毒症时肾组织高迁移率族蛋白 1(HMG 1)的改变及其对TNF α表达的调节作用。动物分为正常对照组 (10只)、CLP组 (2 0只 )及正丁酸钠治疗组 (2 0只 ) ,CLP后 12h和 2 4h处死动物 ,留取肾组织和血标本分别检测HMG 1和TNF αmRNA表达、组织TNF α蛋白水平和血清肌酐含量。结果显示 ,CLP组 12h及 2 4h肾组织HMG 1和TNF αmRNA表达均显著增强 (P <0 0 5或 0 0 1)。正丁酸钠处理可显著抑制CLP后 12h及 2 4h肾组织HMG 1mRNA表达 (P <0 0 5 ) ,并明显下调 2 4h组织TNF αmRNA表达 (P <0 0 5 )及TNF α水平(P <0 0 1) ,同时血清肌酐含量比未治疗组亦显著降低(P <0 0 5或 0 0 1)。提示脓毒症时肾组织HMG 1表达可促进局部TNF α的合成与释放 ,从而诱导脓毒症动物急性肾功能损害。The purpose of this study was to investigate the effect of high mobility group 1 protein (HMG 1) on TNF α expression as well as release in the kidney, and their potential role in the pathogenesis of acute renal injury associated with sepsis. Using a sepsis model by cecal ligation puncture (CLP), 50 male Wistar rats were randomly divided into normal control group ( n =10), CLP group ( n =20), and sodium butyrate treatment group ( n =20). At serial time points animals in each group were sacrificed, and blood as well as kidney tissue samples were harvested to determine HMG 1/TNF α mRNA expression, tissue TNF α protein level, and serum creatinine content. Compared to normal controls, both HMG 1 and TNF α mRNA levels significantly increased in the kidney during 12～24h after CLP ( P <0 05 or 0 01). Treatment with sodium butyrate could markedly inhibit renal HMG 1 mRNA expression at 12h and 24h following CLP (both P <0 05), renal TNF α mRNA (0 486±0 080 vs 0 299±0 044, P <0 05) as well as protein (0 832±0 129 vs 0 349±0 057pg/mg protein, P <0 01) levels were also decreased at 24h. In addition, serum creatinine content in the treatment group was significantly lower than that in CLP group at 12h and 24h, respectively ( P <0 05 or 0 01). These data suggested that elevation of HMG 1 in the kidney might markedly enhance local TNF α expression and release, which would be involved in the development of acute renal injury associated with sepsis.

关 键 词：脓毒症 高迁移率族蛋白-1 肿瘤坏死因子 正丁酸钠 肾功能衰竭 

分 类 号：R631[医药卫生—外科学]