Teoh Narci, Field Jacqueline, Farrell Geoffrey
Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia.
J Hepatol. 2006 Jul;45(1):20-7. doi: 10.1016/j.jhep.2006.01.039. Epub 2006 Mar 20.
BACKGROUND/AIMS: The biological effects of ischaemic preconditioning include NF-kappaB activation, increased TNF synthesis, stimulation of cell cycle entry and hepatoprotection against ischaemia-reperfusion (IR) injury. Low dose TNF initiates the priming phase of liver regeneration via NF-kappaB and IL-6. To determine whether (1) IL-6 is released during preconditioning and confers protection against hepatic IR injury, and (2) IL-6 could mediate the biological effects of preconditioning.
Wildtype (wt) and TNF-/- C57BL6 mice were subjected to 90 min partial hepatic ischaemia and 2-44 h reperfusion with or without prior 10 min ischaemic preconditioning. To restitute liver injury, TNF-/- mice were administered murine TNF 5 microg/kg iv 1 min prior to IR. Murine recombinant IL-6 (500 ng/kg iv) was administered 30 min prior to IR, either to wt mice or to TNF-/--repleted mice; in the latter case, 1 min before preconditioning.
In wt mice, IL-6 attenuated hepatic IR injury and stimulated cell cycle entry. IR injury in TNF-repleted TNF-/- mice was not ameliorated by preconditioning. However, prior IL-6 administration conferred hepatoprotection (IL-6/preconditioned: 349+/-169 U/L vs vehicle/preconditioned: 1250+/-608 U/L, P<0.01).
IL-6 is one likely mediator of the hepatoprotective and pro-proliferative effects of ischaemic preconditioning.
背景/目的：缺血预处理的生物学效应包括核因子κB（NF-κB）激活、肿瘤坏死因子（TNF）合成增加、刺激细胞周期进入以及对缺血再灌注（IR）损伤的肝保护作用。低剂量TNF通过NF-κB和白细胞介素-6（IL-6）启动肝再生的启动阶段。旨在确定：（1）IL-6是否在预处理期间释放并赋予对肝脏IR损伤的保护作用；（2）IL-6是否可介导预处理的生物学效应。
野生型（wt）和TNF基因敲除（TNF-/-）的C57BL6小鼠接受90分钟部分肝脏缺血及2 - 44小时再灌注，有无10分钟缺血预处理。为恢复肝损伤，在IR前1分钟给TNF-/-小鼠静脉注射5微克/千克鼠TNF。在IR前30分钟给wt小鼠或TNF-/-补充小鼠静脉注射鼠重组IL-6（500纳克/千克）；在后者情况下，在预处理前1分钟注射。
在wt小鼠中，IL-6减轻肝脏IR损伤并刺激细胞周期进入。TNF补充的TNF-/-小鼠中的IR损伤未因预处理而改善。然而，预先给予IL-6可赋予肝保护作用（IL-6/预处理组：349±169 U/L vs 载体/预处理组：1250±608 U/L，P<0.01）。
IL-6是缺血预处理的肝保护和促增殖作用的一种可能介质。
