Figure 7. AA blocks the detrimental effect of macrophage activation on hepatocyte viability and improves survival in a lethal hepatic I/R injury model.

(A) RAW264.7 cells transfected with PPARγ siRNA for 48 h prior to AA, or pretreated with GW9662 for 30 min before AA, were followed by LPS/H₂O₂ challenge. Primary hepatocytes were then challenged with these various conditioned supernatants for 6 h prior to harvest for detection of casapse-3 activity. The results are representative of 3 experiments with similar results. * Significant difference (P < 0.05) compared between the indicated groups. NS No significant difference (P > 0.05) between the indicated groups. (B) A lethal hepatic I/R injury model was performed by surgical remove of non-ischemic shunt liver lobes at the end of 90 min ischemia, and the effect of AA on the survival benefit was followed for 7 days after surgery (n=9 of each group). (C) Schematic diagram for the protective effects of AA against hepatic I/R injury. AA leads to activation of PPARγ, which counteracts the KCs-mediated activation of NLRP3 inflammasome via down-regulation of ROS/MAPK and ROS/NF-κB signaling pathway during hepatic I/R, eventually reducing the levels of tissue injury.