内毒素血症时肝组织内促炎因子抗炎因子的变化及其与肝损伤的关系  

The changes in inflammatory and anti-inflammatory cytokine levels in liver tissues and their relation to endotoxin-induced hepatic injury

作　　者：谢国旗[1] 蒋建新[2] 陈永华[2] 刘大维[2] 张宇[2] 朱佩芳[2] 王正国[2] 

机构地区：[1]解放军第一五二医院,河南平顶山467000 [2]第三军医大学大坪医院野战外科研究所,重庆400042

出　　处：《中国危重病急救医学》2001年第11期668-670,共3页Chinese Critical Care Medicine

基　　金：国家自然科学基金资助项目 ( No.39770 313)

摘　　要：目的 :观察内毒素性肝损伤过程中肝组织内致炎因子肿瘤坏死因子α(TNFα)、白介素 6 (IL 6 )和抗炎因子 IL 4、IL 10的变化规律及其与急性肝损伤的关系。方法 :建立小鼠内毒素肝损伤模型 ,酶联免疫吸附法 (EL ISA)检测肝组织内 TNFα、IL 6、IL 4和 IL 10的水平 ,同时观察肝损伤程度。结果 :内毒素肝损伤过程中 ,肝组织内 TNFα和 IL 6水平显著升高 ,均与内毒素呈明显的量效关系 ,肝组织内抗炎症介质IL 4和 IL 10的水平也显著增高 ,抗炎症介质的释放要迟于致炎症介质 ,且随着内毒素剂量的增大 ,抗炎症介质的释放进一步延迟 ,峰值后移 ;随着内毒素剂量的增大 ,血浆丙氨酸转氨酶 (AL T)和总胆红素 (TBIL )进一步升高 ,肝组织结构受损进一步加重。结论 :内毒素致肝损伤后 ,肝组织内抗炎症介质的释放要迟于致炎症介质 ;抗炎症介质释放的延迟可能是导致致炎反应和抗炎反应失衡的原因 。Objective:To investigate the changes in inflammatory and antiinflammatory cytokine levels 〔tumor necrosis factorα(TNFα),interleukin6(IL6),IL4,IL10〕 in liver tissues and their relation to endotoxininduced hepatic injury.Methods:1 mg/kg or 10 mg/kg of E.coli 026:B6 lipopolysaccharide (LPS) were bolus injected to reproduce a mouse model of endotoxemia.TNFα,IL6,IL4 and IL10 levels in hepatic tissues were assayed using enzyme linked immunoadsorbent assay(ELISA).Results:Inflammatory (TNFα and IL6) and antiinflammatory cytokine (IL4 and IL10) levels in hepatic tissues significantly increased in a dose dependent fashion following LPS challenge.The release of the antiinflammatory mediators in the highdose group was shown to be later than that of the lowdose group.The antiinflammatory mediators in the lowdose group reached their peaks at 3 hours and the highdose group reached their peaks at 5 hours.Serum alanine aminotransferase (ALT) and total bilirubin (TBIL) levels significantly increased 1 hour after highdose LPS injection.There were significant differences in serum ALT and TBIL levels between the two groups.The hepatic morphologic alterations were also shown to be paralleled with the dose of LPS.Conclusion:The levels of TNFα,IL6,IL4 and IL10 in hepatic tissues could successively produce after LPS challenge,the unbalance between them may contribute to the immune dysfunction and lead to hepatic injury.

关 键 词：肝损伤 内毒素血症 肿瘤坏死因子-α 白介素 

分 类 号：R631.1[医药卫生—外科学] R363[医药卫生—临床医学]