棕榈酸通过肝细胞氧化应激反应激活炎症小体

Objective To evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes. Methods To test the dose-dependent effect of PA on normal murine hepatocytes AML12, the cells were treated with 0, 0.15, 0.25 and 0.4 mmol/L of palmitic acid (PA). The cells were also divided into blank control group, 0.25 mmol/L PA group and 0.25 mmol/L PA + N-acetylcysteine (NAC) group to examine the effect of reactive oxygen species (ROS) on the activation of inflammasomes. After 24 h of treatment, lipid accumulation, total ROS, mitochondrial ROS, expression and localization of NOX4, and expressions of inflammasomes and IL-1 were detected in the hepatocytes. Results Compared with the control cells, PA treatment of the cells significantly increased cytoplasmic lipid accumulation, concentrations of total ROS (12 463.09 2.72 vs 6691.23 2.45, P=0.00) and mitochondrial ROS (64.98 0.94 vs 45.04 0.92, P=0.00), and the expressions of NOX4, NLRP3, ASC, caspase-1, and IL-1 (1603.521.32 vs 2629.332.57, P=0.00). The mitochondria and NOX4 were found to be co-localized in the cytoplasm. NAC obviously reduced cellular ROS level stimulated by PA (7782.152.87 vs 5445.61.17, P= 0.00) and suppressed the expressions of NLRP3, ASC and caspase-1. Conclusion PA treatment can stimulate lipid accumulation in hepatocytes and induce oxidative stress through NOX4 and mitochondria pathway to activate inflammasomes and stimulate the secretion of IL-1.