目的 基于代谢组学方法探讨黄芪赤风汤（ HQCF）对颈动脉粥样硬化（ CAS）大鼠的肝脏脂质代谢的作用机制。方法 SD大鼠随机分为5组：假手术组、模型组、阿托伐他汀钙片（ Ato，1.8 mg·kg^-1）组和HQCF低、高剂量（1.53、3.06 g·kg^-1）组，采用动脉钳夹术联合高脂饲料喂养建立大鼠CAS模型，假手术组大鼠只做分离颈动脉处理而不使用血管钳，喂食基础饲料。造模时间持续12周，造模结束后ig给药，每天1次，持续28 d。HE染色评估大鼠颈动脉、肝脏的病理学形态；试剂盒法检测大鼠血清肝功能、血脂以及肝脏氧化指标水平；实时荧光定量PCR（qRT-PCR）法测定大鼠肝组织炎性因子基因表达水平； Western blotting法测定大鼠肝组织脂质代谢相关蛋白水平；非靶向代谢组学分析大鼠肝组织代谢物谱。结果 与模型组比较，HQCF组血清三酰甘油（TG）、总胆固醇（ TC）、低密度脂蛋白胆固醇（LDL-C）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ ALT）水平显著下降（P＜0.01）；颈动脉纤维斑块与钙化灶生成明显减少，肝脏组织脂肪变性明显改善；肝组织中超氧化物歧化酶（SOD）活力显著上调、丙二醛（MDA）含量显著下调（P＜0.01），肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-1β基因表达水平显著下调（P＜0.01），脂肪酸合成酶（FAS）、胆固醇调节元件结合蛋白-1c（SREBP-1c）、前蛋白转化酶枯草溶菌素9（PCSK9）蛋白表达水平显著下调且过氧化物酶体增殖物激活受体γ（PPARγ）蛋白表达水平显著上调（P＜0.01）；肝脏非靶向代谢共鉴定出30个差异代谢物，主要富集于初级胆汁酸生物合成、鞘脂代谢、色氨酸代谢等代谢途径。结论 HQCF改善CAS大鼠血脂紊乱的作用机制与调节肝脏组织代谢物水平，从而改善肝脏脂质代谢相关。

Objective To investigate the effect of Huangqi Chifeng Tang (HQCF) on hepatic lipid metabolism in rats with carotid atherosclerosis (CAS) based on metabolomics. Methods SD rats were randomly divided into five groups: sham operation group, model group, atorvastatin calcium tablet (Ato, 1.8 mg·kg^-1) group and HQCF low and high dose (1.53, 3.06 g·kg^-1) groups. The rat CAS model was established by arterial clamp surgery combined with high-fat diet feeding. Rats in the sham operation group only underwent carotid artery separation without using vascular clamps and were fed with basic feed. The modeling period lasted for 12 weeks. After the modeling was completed, intragastric administration was given once a day for 28 d. HE staining was used to evaluate the pathological morphology of the carotid arteries and livers of the rats. The levels of liver function, blood lipids and liver oxidative indicators in rat serum were detected by kit method. The expression levels of inflammatory factor genes in rat liver tissues were determined by real-time fluorescence quantitative PCR (qRT-PCR). The levels of lipid metabolism-related proteins in rat liver tissues were determined by Western blotting. Non-targeted metabolomics was used to analyze the metabolite profiles of rat liver tissues. Results Compared with the model group, the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the serum of the HQCF groups were significantly decreased (P < 0.01); The formation of carotid artery fibrous plaques and calcification foci was significantly reduced, and the fatty degeneration of liver tissue was significantly improved; the activity of superoxide dismutase (SOD) in liver tissue was significantly increased, and the content of malondialdehyde (MDA) was significantly decreased (P < 0.01); The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β genes were significantly decreased (P < 0.01), and the expression levels of fatty acid synthase (FAS), sterol regulatory element-binding protein-1c (SREBP-1c), and proprotein convertase subtilisin/kexin type 9 (PCSK9) proteins were significantly decreased, while the expression level of peroxisome proliferator-activated receptor γ (PPARγ) protein was significantly increased (P < 0.01); A total of 30 differential metabolites were identified in the liver tissues of rats by non-targeted metabolomics, mainly enriched in primary bile acid biosynthesis, sphingolipid metabolism, tryptophan metabolism and other metabolic pathways. Conclusion The mechanism by which HQCF improves lipid disorders in CAS rats is related to the regulation of liver tissue metabolite levels, thereby improving liver lipid metabolism.

R285.5

黑龙江省自然科学基金项目（PL2024H239）