Department of Trauma, Hand and Reconstructive Surgery, Hospitals of the Johann Wolfgang Goethe-University, Frankfurt am Main, 60590 Frankfurt, Germany.
HealthEcon AG, Steinentorstrasse 19, CH-4051 Basle, Switzerland.
Br J Nutr. 2011 Jun 28;105(12):1791-7. doi: 10.1017/S000711451000560X. Epub 2011 Feb 4.
Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0·1 % polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2) mmHg for 60 min and resuscitated. Control groups (sham_ctrl and sham_GTE) underwent surgical procedures without H/R. At 2 h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P < 0·05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P < 0·05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanism.
植物多酚，例如绿茶提取物（GTE），具有很强的抗氧化和抗炎能力，因此在各种急性炎症模型中都具有保护作用。然而，它们在出血/再灌注（H/R）引起的肝损伤中的抗炎作用和可行的机制尚不清楚。我们研究了 GTE 的作用以及 NF-κB 在 H/R 引起的肝损伤发病机制中的作用，以及它们对细胞间黏附分子-1（ICAM-1）表达和中性粒细胞浸润的影响。雌性 Lewis 大鼠在 H/R 前连续 5 天喂食标准膳食（对照，ctrl）或含 0.1%多酚 GTE 的饮食。大鼠的平均动脉压降至 30（sem 2）mmHg 并维持 60min，然后再进行复苏。对照组（sham_ctrl 和 sham_GTE）进行手术但不进行 H/R。再灌注后 2h 采集组织。测定血清丙氨酸氨基转移酶（ALT）和 IL-6。评估肝坏死、ICAM-1 表达和多形核白细胞（PMN）浸润。测定肝 IκBα（磷酸化）的表达。H/R 导致严重的肝损伤，坏死和血清 ALT 水平增加。与 sham 两组相比，H/R 后炎症标志物（血清 IL-6 和肝 PMNL 浸润）升高（P<0.05）。此外，H/R 增加了 IκBα 磷酸化。与 H/R 相比，GTE 给药明显（P<0.05）降低了血清 ALT 和 IL-6 水平、肝坏死以及 PMNL 浸润和 ICAM-1 及磷酸化 IκBα的表达。总之，我们观察到 NF-κB 激活通过上调肝 ICAM-1 表达和随后的 PMNL 浸润，在 H/R 后肝损伤发病机制中发挥重要作用。GTE 预处理通过 NF-κB 依赖性机制预防这种急性炎症模型中的肝损伤。
