目的 探讨玉竹多糖对对乙酰氨基酚诱导的急性肝损伤的预防作用，以及其是否通过调节核因子E2相关因子2（Nrf2）通路抑制铁死亡和炎症反应。方法 采用C57BL/6小鼠ip对乙酰氨基酚建立急性肝损伤模型，玉竹多糖（0.2、0.4、0.8 g/kg）组提前ig 3 d。检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）水平；肝组织苏木素-伊红（HE）染色观察病理改变；测定肝组织亚铁离子含量、氧化应激指标[谷胱甘肽（GSH）、丙二醛（MDA）、超氧化物歧化酶（SOD）]及炎症因子[白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）]水平；Western blotting检测Nrf2、Kelch样ECH相关蛋白1（Keap1）、谷胱甘肽过氧化物酶4（GPX4）、铁死亡抑制蛋白1（FSP1）蛋白表达。结果 与模型组比较，玉竹多糖各剂量组AST、ALT、LDH水平均显著降低（P＜0.05、0.01、0.001），肝坏死和炎症细胞浸润显著减轻。与模型组比较，玉竹多糖0.2、0.4 g/kg组Suzuki评分均显著降低（P＜0.01、0.001）。与模型组比较，玉竹多糖（0.2 、0.4 g/kg）组的IL-1β、IL-6、TNF-α水平均显著下降（P＜0.05、0.01、0.001）。与模型组相比，玉竹多糖（0.2 、0.4 g/kg）组GSH、SOD水平显著上升，Fe²⁺水平显著降低（P＜0.05、0.01、0.001）；玉竹多糖0.2 g/kg组MDA显著降低（P＜0.05）。与模型组相比，玉竹多糖（0.2、0.4 g/kg）组的Nrf2蛋白表达量显著升高（P＜0.05、0.01）；玉竹多糖0.4 g/kg组Keap1、GPX4蛋白表达量显著上调（P＜0.05），玉竹多糖0.2 g/kg组对FSP1蛋白表达量显著升高（P＜0.01）。结论 玉竹多糖通过调节Nrf2通路抑制肝脏铁死亡和炎症反应，从而预防对乙酰氨基酚诱导的急性肝损伤。

Objective To investigate the preventive effect of Polygonatum odoratum polysaccharides on acetaminophen-induced acute liver injury, and to determine whether this effect is mediated by the regulation of the Nrf2 pathway to inhibit hepatic ferroptosis and inflammatory responses. Methods An acute liver injury model was established in C57BL/6 mice by intraperitoneal injection of acetaminophen, Polygonatum odoratum polysaccharides (0.2, 0.4, 0.8 g/kg) groups were administered via oral gavage 3 days in advance. Serum ALT, AST, and LDH levels were measured, pathological changes were observed via HE staining of liver tissue, measured hepatic ferrous iron content, oxidative stress markers (GSH, SOD, MDA), and inflammatory cytokine levels (IL-1β, IL-6, TNF-α), and analyzed protein expression of Nrf2, Keap1, GPX4, and FSP1 via Western blotting. Results Compared with model group, the levels of AST, ALT and LDH in each dose group of Polygonatum odoratum polysaccharides were significantly decreased (P < 0.05, 0.01, 0.001), and the liver necrosis and inflammatory cell infiltration were significantly alleviated. Compared with model group, the Suzuki scores in the Polygonatum odoratum polysaccharides 0.2 and 0.4 g/kg groups were significantly decreased (P < 0.01, 0.001). Compared with model group, the levels of IL-1β, IL-6 and TNF-α in the Polygonatum odoratum polysaccharides 0.2, 0.4 g/kg groups were significantly decreased (P < 0.05, 0.01, 0.001). Compared with model group, the levels of GSH and SOD in the Polygonatum odoratum polysaccharides 0.2, 0.4 g/kg groups were significantly increased, and the Fe²⁺ level were significantly decreased (P < 0.05, 0.01, 0.001), the MDA level in the Polygonatum odoratum polysaccharides 0.2 g/kg group was significantly decreased (P < 0.05). Compared with model group, the protein expression of Nrf2 in the Polygonatum odoratum polysaccharides 0.2, 0.4 g/kg group was significantly increased (P < 0.05, 0.01), the protein expression of Keap1 and GPX4 in the Polygonatum odoratum polysaccharides 0.4 g/kg group was significantly upregulated (P< 0.05), and the protein expression of FSP1 in the Polygonatum odoratum polysaccharides 0.2 group was significantly increased (P < 0.01). Conclusion Polygonatum odoratum polysaccharides prevents acetaminophen-induced acute liver injury by inhibiting hepatic ferroptosis and inflammatory responses through the regulation of the Nrf2 pathway.

R285.5

广西自然科学基金联合专项（2024JJH130036）