目的观察橙皮苷对脂多糖(Lipopolysaccharide,LPS)联合D-氨基半乳糖(D-Galactosamine,D-GalN)所致小鼠急性肝衰竭(Acute hepatic failure,AHF)的保护作用及其机制。方法小鼠腹腔注射LPS(50μg/kg)和D-GalN(800 mg/kg),复制急性肝衰竭模型,分别用橙皮苷(200 mg/kg)或橙皮苷(200 mg/kg)联合锌原卟啉IX(Zinc protoporphyrin IX,ZnPP)(45 mg/kg)干预。造模后6 h检测肝损伤程度和炎症反应强度,48 h统计小鼠死亡率。结果橙皮苷使AHF小鼠血清转氨酶(ALT和AST)水平下降,肝损伤减轻,生存率提高;血清白细胞介素-10(Interleukin-10,IL-10)水平和肝内血红素加氧酶-1(Heme oxygenase-1,HO-1)的表达较AHF小鼠明显增加,肝内HO-1酶活性明显增高;同时,使血清肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)水平、肝组织中Caspase-3蛋白酶和髓过氧物酶(Myeloperoxidase,MPO)活性较AHF小鼠明显降低。ZnPP不影响橙皮苷促进肝内HO-1酶表达,但通过抑制HO-1酶活性,使橙皮苷抗炎和肝损伤保护作用显著降低。结论橙皮苷主要通过诱导HO-1蛋白表达,使HO-1酶活性增强,从而使炎症反应和肝损伤减轻,对LPS联合D-GalN诱导的AHF产生保护作用。 Objective To investigate the protective effect and mechanism of hesperidin on acute hepatic failure (AHF) induced by lipopolysaccharide (LPS) and D-Galactosamine (D-GalN) in mice. Methods Mice were injected with LPS (50μg / kg) and D-GalN (800 mg / kg) intraperitoneally to induce acute hepatic failure. Hesperidin (200 mg / kg) or hesperidin Zinc protoporphyrin IX (ZnPP) (45 mg / kg) intervention. Six hours after modeling, the degree of liver injury and the intensity of inflammatory reaction were detected, and the mortality rate of mice was measured 48 hours later. Results Hesperidin decreased the level of serum ALT and AST in AHF mice, reduced the hepatic injury, and improved the survival rate. The levels of serum interleukin-10 (IL-10) and heme oxygenase The expression of HO-1 (Heme oxygenase-1, HO-1) was significantly higher than that of AHF mice and the activity of HO-1 in the liver was significantly increased. At the same time, the level of serum tumor necrosis factor-α ), The activities of Caspase-3 protease and myeloperoxidase (MPO) in liver tissue were significantly lower than those in AHF mice. ZnPP did not affect the hesperidin to promote the expression of HO-1 enzyme in the liver, but through the inhibition of HO-1 enzyme activity, the protection of hesperidin against inflammation and liver injury was significantly reduced. Conclusion Hesperidin can enhance the activity of HO-1 by inducing the expression of HO-1 protein, thereby reducing the inflammatory reaction and liver injury and protecting the LPS-induced AHF induced by D-GalN.