内毒素预处理对内毒素血症大鼠肝损伤的保护作用  

Protective effects of endotoxin pretreatment on hepatic tissue in rats with endotoxemia

作　　者：陈华文[1] 祝伟[1] 李树生[1] 杨光田[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院ICU,武汉430030

出　　处：《中华急诊医学杂志》2009年第3期262-265,共4页Chinese Journal of Emergency Medicine

基　　金：基金项目：湖北省科技攻关计划项目（2003M301C51）

摘　　要：目的探讨内毒素预处理对内毒素血症大鼠肝损伤的保护作用。方法采用直接注射内毒素的方法建立大鼠急性内毒素血症模型。雄性Wistar大鼠72只，随机分成三组：生理盐水对照组（N组，n=24只）、内素脂多糖（LPS）（L组，n=24只）和LPS预处理组（P组，n=24只），每组又按时间分为2h组、4h组、6h组、12h组4个亚组，每个亚组6只。P组：首次经腹腔注射LPS 0．25mg／kg；24h后再经腹腔注射LPS 0．5mg／kg，其余两组给予等容量生理盐水。第二次腹腔注射72h后，L组和P组经尾静脉一次注射LPS 10mg／kg，N组给予等量生理盐水，L组和P组在注射LPS后2，4，6，12h，N组在注射最后一次NS后2，4，6，12h，各取6只取肝组织制成匀浆检测Toll样受体4（Toll like receptor-4，TLR-4）、核因子-κB（nuclear factor kappa B，NF-κB）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和丙二醛（malondialdehyde，MDA），抽血检测谷丙转氨酶（ALT），谷草转氨酶（AST），取肝脏（肝左上叶）用10％的中性甲醛固定。采用SPSS 13．0统计软件进行单因素方差分析。结果内毒素血症时各时间点肝脏组织TLR-4，NF-κB和TNF-α浓度较对照组显著升高，而内毒素预处理后则有明显下降，其中内毒素血症时4h组肝脏组织TLR-4，NF-κB和TNF-α分别为（38．76±0．67），（170．82±31．40），（293．16±49．49）和（6．263±0．351），显著高于对照组（P〈0．05），而内毒素预处理后上述指标降至（22．32±1．35），（135．55±26．44）和（234．23±44．96），差异有统计学意义（P〈0．05）。结论内毒素预处理可减轻内毒素血症时的肝损伤，其机理可能与肝组织TLR-4，NF-κB和TNF-α的表达减少有关。Objective To investigate the protective effects of endotoxin precondition on hepatic tissue in rats with endotoxemia. Method The models of rats with acute endotoxemia were produced by injecting LPS directly. Seventy-two male wistar rats were randomly divided into three groups： saline control group （N, n = 24）, lipopolysaecharide （LPS） -treated group （L, n = 24）, LPS pretreated group （P, n = 24）. Each group was divided into four subgroups：saline control and lipopolysaccharide （LPS） -treated 2 h,4 h,6 h, 12 h groups and LPS- pretreated 2 h,4 h, 6 h, 12 h groups. Rats in group P were first administered with intropefitoneal injection of 0.25 mg/kg LPS, and after 24 hours, the rats were injected with 0.5 mg/kg LPS. Rats in group N and group L received with an equivalent amount of saline. After 72 hours,rats in group L and group P were intravenously injected with 10 mg/kg LPS,and rats in group N received with an equivalent amount of saline. Six rats were killed at 2,4,6 andl2 hours after injection of IPS in group L and P. The livers were removed for detecting Toll like receptor-4 （TLR-4）, nuclear factor-κB （NF-κB）, tumor Necrosis Factor-apha （TNF-α） and malondialdehyde （MDA）. The blood was drawn for detecting Alamine aminotransferose （ALT） and Aspartate aminotransferose （AST）. The pathological changes of liver were also examined. Software SPSS13.0 was utilized to do ANOVA for statistical analysis. Results The rats exposed to LPS alone demonstrated an increase in TLR-4, NF-κB and TNF-α activity of the liver tissue. Incontrast, the rats exposed to LPS pretreatment exhibited a significant decrease in TLR-4, NF-κB and TNF-α activity. The contents of TLR-4, NF-κB and TNF-α of LPS -treated 4 h group were （38.76 ± 0.67）, 170.82 ± 31.40 ）, 293.16 ± 49.49 ） and（6. 263 ± 0.351 ）, significantly higher than those of the saline control group. The administration of endotoxin pretreatment reduced the indexes to （22.35 ± 1.35）, （ 135.55 ± 26.44 ） and �

关 键 词：内毒素 内毒素血症 预处理 肝损伤 TOLL样受体4 

分 类 号：R285.5[医药卫生—中药学]