HMGB1 translocation and expression is caused by warm ischemia reperfusion injury, but not by partial hepatectomy in rats.

Mechanical injury or ischemia/reperfusion (I/R) injury induces high mobility of group box 1 (HMGB1) translocation and release. However, the surgical procedure itself can initiate pathophysiologic processes causing damage to the respective organ. A liver resection, as an example, leads to portal hyperperfusion injury of the remnant liver. Therefore, we aimed to elucidate the impact of different hepatic surgical injury models on cellular localization and expression of HMGB1. Focal warm I/R injury was induced by clamping the vascular blood supply to the median and left lateral liver lobes for 90 min followed by 0.5 h, 6 h and 24 h reperfusion, as reported previously. Liver injury by PH was induced by subjecting rats to 30%, 70% or 90% partial hepatectomy (PH) followed by a 24 h observation period. Additional 12 rats were subjected to 90% PH and sacrificed at 1 h and 6 h to investigate the expression and release pattern of HMGB1. Elevation of serum liver enzymes indicating hepatic injury peaked at 6 h and recovered thereafter in models, warm I/R injury and PH. Liver injury was confirmed by liver histology. HMGB1 was translocated from the nucleus to the cytoplasm in livers subjected to warm I/R; but not in livers subjected to PH. Both protein and mRNA expression of HMGB1 were significantly up-regulated in livers subjected to warm I/R. In contrast, neither 30% PH, 70% PH nor 90% PH caused an elevation of hepatic HMGB1 mRNA and protein expression. High serum levels of HMGB1 (30 ng/ml) were measured at 0.5 h reperfusion period after warm I/R, much lower levels thereafter (<5 ng/ml). Similar low serum levels were measured at all time points after 90% PH. Subsequently expression levels of TNF-a should be changed to tumor necrosis factor-alpha (TNF-α) reached a peak (26-fold elevation) at 6 h and decreased down to 5-fold at 24 h after warm I/R. TNF-α expression levels after PH never exceeded a 5-fold elevation. In conclusion, HMGB1 translocation and expression depends on the type of liver injury as it is induced by ischemia, but not by liver resection/hyperperfusion. These results suggest that HMGB1 may be used as molecular marker to visualize ischemic damage. Mechanic injury in hepatic surgery is associated with focal warm ischemia, and thereby HMGB1 translocation reflects surgical quality in experimental PH. Expression of hepatic TNF-α follows the kinetic pattern of HMGB1, pointing to a muss less pronounced inflammatory response after successful PH compared to warm I/R injury.