目的 基于血清、肝脏及粪便代谢组学技术，探讨绞股蓝总苷调血脂的代谢调节机制。方法 采用高脂饮食建立大鼠高脂血症模型，将32只雄性SD大鼠随机分为对照组、模型组、阿托伐他汀（10 mg/kg）组和绞股蓝总苷（150 mg/kg）组。连续给药8周后检测大鼠体质量、血脂水平。利用超高效液相色谱-四极杆-飞行时间质谱技术分析血清、肝脏和粪便中的代谢物，并结合多元统计分析筛选差异代谢物。结果 绞股蓝总苷可显著降低高脂血症大鼠血清中总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平（P＜0.05、0.01）。代谢组学分析显示，绞股蓝总苷能够显著回调模型大鼠的内源性代谢谱，从血清、肝脏和粪便中分别筛选出30、27、19个差异代谢物，主要包括溶血磷脂酰胆碱、不饱和脂肪酸及其衍生物、胆汁酸、氨基酸及其衍生物等，涉及甘油磷脂代谢、亚油酸与花生四烯酸代谢、不饱和脂肪酸生物合成、初级胆汁酸代谢及色氨酸代谢等通路。除肝脏中甘氨胆酸和甘氨熊去氧胆酸在绞股蓝总苷干预后仍呈升高趋势外，其余差异代谢物均恢复至接近正常水平。结论 绞股蓝总苷可通过多靶点调控脂质代谢网络发挥调血脂作用，其机制与干预溶血磷脂酰胆碱代谢、亚油酸与花生四烯酸代谢、胆汁酸代谢及色氨酸代谢等通路有关，系统揭示了绞股蓝总苷对高脂血症大鼠内源性代谢的整体调节作用。

Objective To investigate the hypolipidemic effects of gypenosides based on serum, liver and fecal metabolomics techniques. Methods A high-fat diet was used to establish a hyperlipidemia model in rats, with 32 male SD rats randomly divided into control group, model group, atorvastatin (10 mg/kg) group and gypenosides (150 mg/kg) group. After eight weeks of continuous administration, body weight and blood lipid levels were measured. Metabolites in serum, liver and feces were analyzed using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, and differential metabolites were screened through multivariate statistical analysis. Results Gypenosides significantly reduced levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in serum of hyperlipidemic rats (P < 0.05, 0.01). Metabolomics analysis revealed that gypenosides effectively normalized the endogenous metabolic profile of model rats, identifying 30, 27, 19 differential metabolites in serum, liver and feces, respectively, primarily including lysophosphatidylcholine, unsaturated fatty acids and derivatives, bile acids, and amino acids and derivatives, linked to glycerophospholipid, linoleic/arachidonic acid, unsaturated fatty acid, primary bile acid biosynthesis, and tryptophan metabolism. Except for glycoursodeoxycholic acid and glycylglycoursodeoxycholic acid in liver, which still showed an increasing trend after gypenosides intervention, all other differential metabolites returned to near-normal levels. Conclusion Gypenosides modulate blood lipids by regulating the lipid metabolism network through multiple targets, with mechanisms related to intervention in lysophosphatidylcholine metabolism, linoleic acid and arachidonic acid metabolism, bile acid metabolism and tryptophan metabolism pathways, systematically revealing the overall regulatory effect of gypenosides on endogenous metabolism of hyperlipidemic rats.

R285.5

湖北民族大学湖北省肾脏病临床医学研究中心项目(OIR202302Z); 国家自然科学基金资助项目(82160804); 恩施州科技计划项目(D20230085); 湖北民族大学创新创业项目(202210517008);横向科研项目(H24013)