【摘要】 目的:观察脂多糖(LPS)预处理后白细胞介素-1受体相关激酶-4(IRAK-4)表达水平在大鼠肝脏缺血再灌注(I/R)早期的变化,探讨LPS预处理减轻肝脏缺血再灌注损害(I/R I)的相关机制。方法:雄性SD大鼠,随机分为正常对照组,缺血再灌注组(I/R组)和LPS预处理组(LPS组)。正常对照组未予任何处理;LPS组第1 d经尾静脉给予脂多糖0.1mg.kg-1,第2、3、4、5 d给予0.5 mg.kg-1;I/R组给予等体积0.5 mL无菌PBS液。第8 d,建立肝脏缺血再灌注模型。再灌注后0 m in、60 m in及180 m in,蛋白免疫印记法及逆转录-聚合酶链式反应测定肝组织的IRAK-4蛋白和mRNA表达水平;酶连免疫吸附法检测肝组织NF-κB活性及血清TNF-α含量。结果:再灌注0 m in,IRAK-4蛋白与mRNA表达水平依次为LPS组>I/R组>正常对照组(P<0.01),NF-κB活性以及TNF-α含量LPS组与I/R组差异无显著(P>0.05),但均高于正常对照组(P<0.01);再灌注后60 m in及180m in,LPS组的IRAK-4蛋白与mRNA表达水平,NF-κB活性以及TNF-α含量却明显低于I/R组(P<0.01)。结论:抑制IRAK-4表达是LPS预处理减轻肝脏I/R I的重要机制之一。更多还原

【Abstract】 AIM: To observe the changes of interleukin1 receptor associated kinase-4(IRAK-4) in ischemia/reperfusion(I/R) liver pretreated with lipopolysaccharide(LPS) and to explore the protective mechanisms of LPS pretreatment against hepatic I/R injury.METHODS: Male Sprague-Dawley rats,weighing 240-280 g,were divided into three groups: control,ischemia/reperfusion group(I/R group) and LPS-pretreated group(LPS group).On the first day,LPS group received 0.1 mg/kg LPS via the tail vein,followed by 0.5 mg/kg on the 2nd,3rd,4th and 5th day.I/R group received the equivalent volumes(0.5 mL) of sterile PBS.Experiments of I/R injury was induced by temporary ischemia of the left lateral liver lobe for 90 min followed by 3 h reperfusion on 2 days after the last LPS treatment.At 0 min,60 min and 180 min after reperfusion,the expression of IRAK-4 gene and protein level were determined by RT-PCR and Western blotting.The activity of NF-κB and the serum TNF-α level were also detected by ELISA.RESULTS: Although the level of IRAK-4 gene and protein were higher in the LPS group than that in I/R group and control group(P<0.01),no difference of the activities of NF-κB and the TNF-α level was observed between the LPS group and I/R group(P>0.05) at 0 min after reperfusion.However,all those indexes were evidently lower in the LPS group than those in I/R group(P<0.01) at 60 min and 180 min after reperfusion.CONCLUSION: This data suggests that the protective effects induced by LPS pretreatment against hepatic I/R injury may be via down-regulation of IRAK-4 expression.更多还原