橙皮苷对小鼠急性肝衰竭的保护作用及其机制

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。

Protective Effect of Hesperidin on Acute Hepatic Failure in Mice and Relevant Mechanism

Objective To observe the protective effect of hesperidin on acute hepatic failure(AHF) caused by lipopolysaccharide(LPS) combined with D-galactosamine(D-GalN) in mice and investigate the relevant mechanism.Methods Mouse model of AHF was copied by injection i.p.with LPS(50 μg / kg) and D-GalN(800 mg / kg),and treated by hesperidin(200 mg / kg) or hesperidin(200 mg / kg) combined with zinc protoporphyrin Ⅺ(ZnPP,45 mg / kg).The degrees of hepatic injury and inflammatory reaction were determined 6 h,while the death rate of mice 48 h after the model was copied.Results Hesperidin decreased the serum transaminase,relieved the hepatic injury and increased the survival rate of mice with AHF.Compared with those without treatment,the IL-10 level in sera as well as the heme oxygenase-1(HO-1) expression level and activity in liver of mice with AHF treated by hesperidin increased significantly,while tumor necrosis factor-α(TNF-α) level in sera as well as caspase-3 and myeloperoxidase(MPO) activities in liver tissues decreased significantly.ZnPP showed no influence on the promoting effect of hesperidin on HO-1 expression in liver,however,it down-regulated the protective effect of hesperidin against inflammation and hepatic injury significantly by inhibiting HO-1 activity.Conclusion Hesperidin increased the HO-1 activity by inducing HO-1 expresssion,thereby relieved inflammatory reaction and hepatic injury and protected mice against LPS / D-GalN-induced AHF.