为探讨氧化三甲胺（TMAO）驱动PERK/FOXO1轴对棕榈酸（PA）诱导人肝癌（HepG2）细胞HDL代谢的影响。通过体外培养HepG2细胞，CCK-8分别检测PA、TMAO、DMB（3，3-二甲基-1-丁醇）对细胞的抑制率，取最终浓度进行后续实验；生化试剂盒法检测细胞TG、TC、HDL-C、LDL-C含量变化；油红O染色法检测细胞脂质沉积情况；Western Blot法检测细胞PERK、FOXO1 SR-BI、HL、APOA-1蛋白表达情况。选取终浓度0.2 mmol/L PA、10μ mol/L DMB、0.4 mmol/L TMAO进行最终实验，随机分为6组：对照组、DAB对照组（10 μmol/L DAB，TMAO抑制剂）、PA诱导组（0.2 mmol/L棕榈酸）、PA+DAB对照组（0.2 mmol/L PA+10 μmol/L DAB）、TMAO组（0.2 mmol/L PA+0.4 mmol/L TMAO）、TMAO+DAB组（0.2 mmol/L PA+0.4 mmol/L TMAO+10 μmol/L DAB）。结果表明：与对照组比较，PA组和TMAO组TG、TC、LDL-C含量明显升高（P<0.01），HDL-C含量明显降低（P<0.01），细胞脂质沉积明显，细胞内p-PERK、FOXO1蛋白表达升高（P<0.05，P<0.01），SR-BI、HL、APOA-1蛋白表达显著降低（P<0.01）；与PA组比较，TMAO组以上各指标变化进一步加重（P<0.05，P<0.01）；与TMAO组比较，给予抑制剂后，TMAO+DMB组各指标变化明显得到改善（P<0.05，P<0.01）。可见TMAO可通过驱动PERK/FOXO1轴达到调控下游HDL代谢的作用。

To investigate the effect of trimethylamine oxide (TMAO)-driven PERK/FOXO1 axis on HDL metabolism in palmitic acid (PA)-induced human hepatocellular carcinoma (HepG2) cells. HepG2 cells were cultured in vitro, and the inhibition rates of PA, TMAO, and DMB (3,3-dimethyl-1-butanol, a TMAO inhibitor) were detected by CCK-8, respectively, and the final concentrations were taken for the subsequent experiments. Changes in the cellular TG, TC, HDL-C, and LDL-C contents were detected by the biochemical kit method, and cellular lipid deposition was detected by the Oil Red O staining method. Western Blot method was used to detect cellular PERK, FOXO1 SR-BI, HL, APOA-1 protein expression. The final concentration of 0.2 mmol/L PA, 10 μmol/L DMB, and 0.4 mmol/L TMAO were selected for the final experiment, and were randomly divided into 6 groups: Control group, DAB control group (10 μmol/L DAB, TMAO inhibitor), PA-induced group (0.2 mmol/L palmitic acid), PA + DAB control group (0.2 mmol/L PA + 10 μmol/L DAB), TMAO group (0.2 mmol/LPA + 0.4 mmol/L TMAO), TMAO + DAB group (0.2 mmol/L PA +0.4mmol/L TMAO + 10 μmol/L DAB). The results show that compared with the Control group, the PA and TMAO groups show significantly higher TG, TC, and LDL-C content (P <0.01), significantly lower HDL-C content (P < 0.01), significant cellular lipid deposition, elevated intracellular p-PERK and FOXO1 protein expression (P < 0.05, P < 0.01), and SR-BI, HL, APOA-1 protein expression is significantly reduced (P <0.01). Compared with the PA group, the changes of the above indexes in the TMAO group are further aggravated (P <0.05, P < 0.01). Compared with the TMAO group, the changes of the indexes in the TMAO + DMB group are significantly improved after the administration of inhibitors (P <0.05, P < 0.01). It can be seen that TMAO can achieve the role of regulating downstream HDL metabolism by driving the PERK/FOXO1 axis.