Glanemann Matthias, Vollmar Brigitte, Nussler Andreas K, Schaefer Thilo, Neuhaus Peter, Menger Michael D
Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Berlin, Germany.
J Hepatol. 2003 Jan;38(1):59-66. doi: 10.1016/s0168-8278(02)00327-6.
BACKGROUND/AIMS: Ischemic preconditioning (IP) is known to protect hepatic tissue from ischemia-reperfusion injury. However, the mechanisms involved are not fully understood yet.
Using intravital multifluorescence microscopy in the rat liver, we studied whether IP exerts its beneficial effect by modulating postischemic Kupffer cell activation, leukocyte-endothelial cell interaction, microvascular no-reflow, mitochondrial redox state, and, thus, tissue oxygenation.
Portal triad cross-clamping (45 min) followed by reperfusion induced Kupffer cell activation, microvascular leukocyte adherence, sinusoidal perfusion failure (no-reflow) and alteration of mitochondrial redox state (tissue hypoxia) (P<0.05). This resulted in liver dysfunction and parenchymal injury, as indicated by decreased bile flow and increased serum glutamate dehydrogenase (GLDH) levels (P<0.05). IP (5 min ischemia and 30 min intermittent reperfusion) was capable to significantly reduce Kupffer cell activation (P<0.05), which was associated with a slight attenuation of leukocyte adherence. Further, IP markedly ameliorated sinusoidal perfusion failure (P<0.05), and, thereby, preserved adequate mitochondrial redox state (P<0.05). As a consequence, IP prevented the decrease of bile flow (P<0.05) and the increase in serum GLDH levels (P<0.05).
IP may exert its beneficial effects on hepatic ischemia-reperfusion injury by preserving mitochondrial redox state, which is guaranteed by the prevention of reperfusion-associated Kupffer cell activation and sinusoidal perfusion failure.
背景/目的：缺血预处理（IP）已知可保护肝组织免受缺血再灌注损伤。然而，其涉及的机制尚未完全清楚。
利用大鼠肝脏活体多荧光显微镜，我们研究了IP是否通过调节缺血后库普弗细胞激活、白细胞-内皮细胞相互作用、微血管无复流、线粒体氧化还原状态以及组织氧合来发挥其有益作用。
门静脉三联钳夹（45分钟）后再灌注诱导了库普弗细胞激活、微血管白细胞黏附、肝血窦灌注衰竭（无复流）以及线粒体氧化还原状态改变（组织缺氧）（P<0.05）。这导致了肝功能障碍和实质损伤，表现为胆汁流量减少和血清谷氨酸脱氢酶（GLDH）水平升高（P<0.05）。IP（5分钟缺血和30分钟间歇性再灌注）能够显著降低库普弗细胞激活（P<0.05），这与白细胞黏附的轻微减轻相关。此外，IP明显改善了肝血窦灌注衰竭（P<0.05），从而维持了适当的线粒体氧化还原状态（P<0.05）。结果，IP预防了胆汁流量的减少（P<0.05）和血清GLDH水平的升高（P<0.05）。
IP可能通过维持线粒体氧化还原状态对肝缺血再灌注损伤发挥有益作用，这是通过预防再灌注相关的库普弗细胞激活和肝血窦灌注衰竭来保证的。
