Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Drackendorfer straße1, 07747, Jena, Germany.
Histochem Cell Biol. 2011 May;135(5):443-52. doi: 10.1007/s00418-011-0802-6. Epub 2011 Mar 24.
High mobility group box 1 (HMGB1) acts as an early mediator in inflammation and organ injury. Ischemia reperfusion (I/R) injury induces HMGB1 translocation and expression in ischemic areas. However, it is unknown whether selective warm liver I/R injury also induces the expression of HMGB1 in non-ischemic lobes. The present study aimed to test the hypothesis that selective liver I/R injury also causes HMGB1 translocation and up-regulates its expression in non-ischemic liver areas. In the present study, selective I/R injury was induced by clamping the median and left lateral liver lobes for 90 min followed by 0.5, 6 and 24 h reperfusion. We used male inbred Lewis rats; six animals for each point in time and six animals for the normal control group. Selective hepatic I/R injury induced morphological changes not only in ischemic lobes but also in non-ischemic lobes. HMGB1 translocation and expression was increased in a time-dependent manner in the ischemic lobes, and increased in with delayed onset in the non-ischemic lobes. Serum HMGB1 levels were increased after reperfusion. Furthermore, liver I/R injury up-regulated the expression of HMGB1 receptors (Toll-like receptor 4 and receptor for advanced glycation end products and pro-inflammatory cytokines (Tumor necrosis factor-alpha and interleukin-6) in both ischemic lobes, however, the up-regulation of these cytokines was more prominent in the ischemic lobes. In conclusion, selective warm I/R induces a substantial "sympathetic/bystander" effect on the non-ischemic lobes in terms of HMGB1 translocation and local cytokine production.
高迁移率族蛋白 B1（HMGB1）作为炎症和器官损伤的早期介质发挥作用。缺血再灌注（I/R）损伤可诱导缺血区域 HMGB1 的易位和表达。然而，尚不清楚选择性温肝 I/R 损伤是否也会导致非缺血叶中 HMGB1 的表达。本研究旨在检验以下假设：选择性肝 I/R 损伤也会导致 HMGB1 易位，并上调非缺血肝区的表达。在本研究中，通过夹闭中肝叶和左外侧肝叶 90 分钟，然后再灌注 0.5、6 和 24 小时来诱导选择性 I/R 损伤。我们使用雄性近交系 Lewis 大鼠；每个时间点 6 只动物，正常对照组 6 只动物。选择性肝 I/R 损伤不仅在缺血叶，而且在非缺血叶也引起形态学变化。HMGB1 的易位和表达在缺血叶呈时间依赖性增加，而非缺血叶则延迟发生。再灌注后血清 HMGB1 水平升高。此外，肝 I/R 损伤上调了缺血叶和非缺血叶 HMGB1 受体（Toll 样受体 4 和晚期糖基化终产物受体）以及促炎细胞因子（肿瘤坏死因子-α和白细胞介素-6）的表达，但缺血叶的上调更为明显。总之，选择性温 I/R 会导致非缺血叶的 HMGB1 易位和局部细胞因子产生产生实质性的“交感/旁观者”效应。
