IRAK-4活性在脂多糖预处理减轻肝脏缺血再灌注损害中作用的实验研究  

Role of IRAK-4 activity in inhibitory effects of lipopolysaccharide pretreatment on hepatic ischemia/reperfusion injury

作　　者：刘作金[1] 刘长安[1] 游海波[1] 陈先锋[1] 李旭宏[1] 龚建平[1] 

机构地区：[1]重庆医科大学附属第二医院肝胆外科,重庆400010

出　　处：《中国病理生理杂志》2006年第11期2123-2126,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30471969No.30500473);重庆市卫生局科研基金重点资助项目(No.03-1-001);重庆市自然科学基金资助项目(2005BB5242)

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。AIM ： To observe the changes of interleukin - 1 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 - KB 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.

关 键 词：再灌注损伤 脂多糖类 肝 白细胞介素-1受体相关激酶-4 

分 类 号：R363[医药卫生—病理学]