内毒素预处理对内毒素血症大鼠肝损伤的保护作用

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市大鼠急性内毒素血症模型.雄性Wistar人鼠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(IPS)(L组,n=24只)和LPS预处理组(P组,n=24只),每组义按时间分为2 h组、4 h组、6 h组、12 h组4个亚组,每个亚组6只.P组:首次经腹腔注射LPS 0.25mg/kg;24 h后再经腹腔注射IPSO.5 mg/kg,其余两组给予等容量生理盐水.第二次腹腔注射72 h后,L组和P组经尾静脉一次注射LPS 10 mg/kg,N组给予等量生理盐水,L组和P组在注射LPS后2,4,6,12 h,N组在注射最后一次NS后2,4,6,12 h,各取6只取肝组织制成匀浆检测Toll样受体4(Toll likereceptor-4,TLR-4)、核因子-кB(nuclear factor kappa B,NF-кB)、肿瘤坏死因子-α(tulnor necrosis factor-a,TNF-α)和丙二醛(malondiahtehyde,MDA),抽血检测谷丙转氨酶(ALT),谷草转氨酶(ASF),取肝脏(肝左上叶)用10%的中性甲醛固定.采用SPSS 13.0统汁软件进行单因素方差分析.结果 内毒素血症时符时间点肝脏组织TLR-4,NF-кB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4 h组肝脏组织TLR-4,NF-кB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-кB和TNF-α的表达减少有关.

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

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),lipopolysaccharide (LPS)-treated group(L,n=24),LPS pretreated group(P,n=24).Each group was divid-ed 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 introperitoneal 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 intravenonsly 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 and 12 hours after injection of LPS in group L and P.The hvers were removed for detecting Toll like receptor-4 (TLR-4),nuclear factor-кB(NF-кB),tumor Necrosis Factor-apha(TNF-α)and malondialdehyde(MDA).The blood was drawn for detecting Alamine aminotmnsferose (ALT) and Aspartate aminotransferose (AST).The patho-logical 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-кB and TNF-α activity of the liver tissue.Incontrast.the rats exporsed 10 LPS prelreatment exhibited a significant decrease in TLT-4,NF-кB and TNF-α activity.The contents of TLR-4,NF-кB and TNF-α of LPS-treated 4 h groupwere,(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(234.23±44.96),respectively(P＜0.05).Conclusions TLR-4,NF-кB and TNF-α take part in the progress of hepatic injury in rats with endotoxemia.Endotoxin pretreatment can eliminate hepatic injury and protect the hepatic tissue by downmgulating the levels of TLR-4.NF-кB and TNF-α.