目的 基于代谢组学方法探讨芹菜素对高脂血症小鼠的肝脏保护作用及机制。方法 将 C57BL/6 小鼠 随机分为 4 组，分别为正常组、模型组、非诺贝特组（26.0 mg·kg-1 ）和芹菜素组（12.5 mg·kg-1 ），每组 6 只， 灌胃给药，每日 1 次，连续给药 5 d。给药第 3 天，采用单次肌肉注射 0.12 g·mL-1 浓度的 Triton WR-1339 （5 mL·kg-1 ）诱导急性高脂血症小鼠模型。采用全自动酶标仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）含量； HE 染色法观察肝脏组织病理变化。采用 UPLC-Q-TOF-MS/MS 分析小鼠肝脏组织样品，通过主成分分析 （PCA）、偏最小二乘法判别分析（PLS-DA）、正交偏最小二乘法判别分析（OPLS-DA）等多元统计分析筛选差异 代谢物。将差异代谢物的质谱信息通过 HMDB、METLIN 以及 KEGG 等在线数据库结合相关文献鉴定出潜在差 异代谢物。将已鉴定的潜在差异化合物导入 MetaboAnalyst 平台进行代谢通路分析。结果 与正常组比较，模 型组小鼠的血清 TC、TG 水平显著升高（P＜0.01），肝组织的细胞排列不规律，脂肪空泡和炎性细胞浸润明显。 与模型组相比，芹菜素组的血清 TC、TG 水平有降低，但差异无统计学意义（P＞0.05）；肝脏组织脂肪病变得 到明显改善，脂肪空泡和炎性细胞浸润均明显减少。共筛选出 35 个潜在差异性标志物，芹菜素给药后有 26 个 具有回调趋势。差异代谢物共影响了 8 条代谢通路，其中 2 条主要代谢通路（P＜0.05）分别为泛酸盐和辅酶 A （CoA）生物合成、花生四烯酸代谢。结论 芹菜素对高脂血症小鼠具有一定肝脏保护作用，其作用机制可能与 调控肝脏炎症反应及脂质代谢相关通路有关。

Objective To investigate the protective effect and mechanism of apigenin on the liver of hyperlipidemic mice based on metabolomics methods. Methods C57BL/6 mice were randomly divided into four groups including blank，model，fenofibrate （26.0 mg·kg-1 ），and apigenin （12.5 mg·kg-1 ） groups，with six mice in each group. Each group was treated with corresponding drug by gavage once a day for five days. On the third day of administration，the mouse model of acute hyperlipidemia was induced by a single intramuscular injection of Triton WR-1339 （5 mL·kg-1 ） at a concentration of 0.12 g·mL-1 . Biochemical indexes such as TC and TG in mice serum were measured by using a fully automatic microplate reader. HE staining was used to observe pathological changes in liver tissue. UPLC-Q-TOF-MS/MS technology was applied to analyze liver tissue samples. Differential metabolites were screened by using multivariate statistical analysis methods such as PCA，PLS-DA，and OPLS-DA. Then we ran the mass spectrometry information of these metabolites through online databases including HMDB，METLIN and KEGG，as well as combined with relevant literature to obtain the potential differential metabolites. The identified potential differential compounds were imported into the MetaboAnalyst platform for metabolic pathway analysis. Results Compared with the blank group，TC and TG levels in mice serum of model group increased obviously （P＜ 0.01） . Irregular arrangement of liver cells，fat vacuoles and infiltration of inflammatory cells were found. Compared with the model group，TC and TG levels in mice serum of apigenin group decreased （P＞0.05）. Fatty lesions in liver tissue were significantly improved， and fat vacuoles and inflammatory cell infiltration were significantly reduced. A total of 35 differential metabolites were screened. Twenty-six differential metabolites showed callback trend after apigenin treatment. Eight metabolic pathways were obviously affected， among which pantothenate and CoA biosynthesis，as well as arachidonic acid metabolism are two main metabolic pathways （P＜0.05）. Conclusion Apigenin exhibits a certain protective effect on liver of hyperlipidemic mice，and its mechanism may be related to regulating liver inflammatory response and lipid metabolism-related pathways.

R285.5

广东省医学科学技术研究基金项目（B2021260，A2023050）