肝内抗炎与致炎反应变化及其与内毒素肝损伤的关系  

Kinetics of intrahepatic pro-inflammatory and anti-inflammatory responses and their relation to endotoxin-induced hepatic damage

作　　者：蒋建新[1] 谢国旗[1] 陈永华[1] 邱俊[1] 刘大为[1] 朱佩芳[1] 王正国[1] 周继红[1] 张洪杰[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所,重庆400042

出　　处：《中华肝胆外科杂志》2001年第6期368-371,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：国家重点基础研究发展项目 ( 6 19990 5 42 0 0 ) ;国家自然科学基金资助 ( 39770 313) ;军队医药卫生杰出中青年科研基金资助项目

摘　　要：目的　探讨内毒素致肝损伤过程中肝内致炎与抗炎反应的变化规律及其作用 ,为深入阐明内毒素肝损伤的发病机制提供实验依据。方法　于尾静脉注入不同剂量内毒素 (E .coli 0 2 6 :B6 )复制内毒素血症或休克模型。采用ELISA法检测小鼠肝组织内TNFα、IL 6、IL 4、IL 10含量 ,并分析其与肝损害的关系。结果　注射LPS后 1h ,低剂量和高剂量组肝组织内致炎介质TNFα、IL 6水平即显著增高 ,其中IL 6在注射LPS后 3h达峰值 ,至 8h仍显著高于对照组。高剂量组肝内TNFα、IL 6水平明显高于低剂量组。抗炎细胞因子IL 4、IL 10水平在注射LPS后 1h虽均无明显变化 ,但至 3h ,两组肝内IL 4、IL 10水平都显著升高 ,并在 8h仍显著高于对照组 ,其中高剂量组肝内IL 4 ,IL 10水平也明显高于低剂量组。肝内致炎和抗炎介质变化与肝组织结构受损、肝功能障碍呈一致性改变。结论　内毒素致肝损伤过程中 ,肝内相继发生致炎与抗炎反应 ,两者相互作用失衡是导致内毒素肝损伤的重要机制。因此 ,在内毒素肝损伤的防治中应考虑到局部抗炎与致炎反应的综合作用。Objective To investigate change rules and roles of intrahepatic pro-inflammatory and anti-inflammatory responses to provide experimental evidence for further elucidation of the pathogenesis of endotoxin-induced hepatic damage. Methods Mouse model of endotoxemia or endotoxin shock was produced by injection of different doses of lipopolysaccharide (LPS, E. coli O26:B6) via tail vein. The levels of TNFa, IL-6, IL-4 and IL-10 in liver tissue were assayed with ELISA. Results The levels of TNFa and IL-6 in liver tissue in both low- and high-dose groups were shown to be increased 1 hour after the injection of LPS. IL-6 level in both groups peaked at the 3rd hour and was significantly higher than that in the control group at the 8th hour. The levels of TNFa and IL-6 in liver tissue were markedly higher in high-dose group than in low-dose group. The levels of IL-4 and IL-10 in liver tissue in both groups, though being not significantly changed 1 hour after the injection of LPS, were significantly increased at the 3rd hour and still markedly higher at the 8th hour. The levels of IL-4 and IL-10 in liver tissue in high-dose group were significantly higher than those in low-dose group. The changes in intrahepatic pro-inflammatory and anti-inflammatory cytokines were shown to be paralleled to hepatic structural damage and dysfunction. Conclusions Pro-inflammatory and anti-inflammatory responses successively occurred during endotoxin-induced hepatic damage. The imbalance between their reaction may be the important mechanism for endotoxin-induced hepatic damage. Therefore, the synthetic action of local pro-inflammatory and anti-inflammatory responses should be taken into account in the treatment of endotoxin-induced hepatic disease.

关 键 词：内毒素类 炎症 肝 抗炎症反应 致炎反应 肝损伤 CARS 

分 类 号：R657.3[医药卫生—外科学]