目的 基于脂质组学探讨葛根芩连汤改善高脂饮食诱导大鼠代谢相关脂肪性肝病（MAFLD）的作用及机 制。方法 将雄性 SD 大鼠随机分为造模组（50 只）及空白组（10 只），空白组给予普通饲料喂养，造模组给予 高脂饲料喂养；连续饲养 12 周后，将造模组大鼠随机分为模型组、阳性药组（罗格列酮 5 mg·kg -1 ）以及葛根芩 连汤低、中、高剂量组（1.65、4.96、14.86 g·kg -1 ），每组 10 只。除空白组外，其余各组继续给予高脂饲料喂 养；同时按照上述剂量灌胃给药（10 mL·kg -1 ），每天 1 次，连续给药 16 周。采用油红 O 染色法观察肝脏组织 脂肪变性情况；检测大鼠血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白 胆固醇（LDL-C）、胰岛素（Fins）及空腹血糖（FBG）水平，计算胰岛素抵抗指数（HOMA-IR）；基于 UPLC- QTOF-MS 技术进行肝脏脂质组学分析，筛选差异脂质代谢物，并进行代谢通路富集分析。 结果 （1）与空白 组比较，模型组大鼠的体质量、HOMA-IR 及 FBG、TG 水平显著升高（P＜0.05，P＜0.01）；肝细胞明显肿胀， 细胞质内明显可见脂肪空泡，脂滴融合导致细胞核偏位，甚至细胞核消失，肝脏组织内可见弥漫分布的大油滴 及微小脂滴，并散布全肝，肝细胞有明显的炎症变化。与模型组比较，葛根芩连汤低、中剂量组大鼠的体质 量、FBG 水平显著降低（P＜0.05，P＜0.01），葛根芩连汤低、高剂量组大鼠的 TC、LDL-C 水平显著降低（P＜ 0.05，P＜0.01），葛根芩连汤低剂量组大鼠的 HOMA-IR 明显降低（P＜0.05），葛根芩连汤中剂量组大鼠的 TG 水平明显降低（P＜0.05）；葛根芩连汤各剂量组大鼠肝脏组织内弥漫分布的脂滴数量和面积明显减少。（2）筛选 出葛根芩连汤干预 MAFLD 大鼠的潜在脂质代谢标志物 16 个，葛根芩连汤可以提高 MAFLD 大鼠肝脏组织 PC [22∶6（4Z，7Z，11E，13Z，15E，19Z）-2OH（10S，17）/14∶1（9Z）]、PS[20∶3（8Z，11Z，14Z）/LTE4]、PA[20∶4（5Z，7E， 11Z，14Z）-OH（9）/i-17∶0]等磷脂水平，降低其肝脏组织 Cer （d16∶1/16∶0），LysoPC[18∶4（6Z，9Z，12Z，15Z）/0∶0] 等脂质代谢物水平。差异脂质代谢物主要富集在以下 4 条代谢通路：甘油磷脂代谢、鞘脂代谢、肌醇磷酸盐代 谢、糖基磷脂酰肌醇锚生物合成。结论 葛根芩连汤能够显著改善 MAFLD 大鼠的肝脏脂肪变性、血清脂质代 谢紊乱及胰岛素抵抗，可能与调控甘油磷脂代谢、鞘脂代谢等途径，改善肝脏中磷脂酰胆碱、磷脂酰肌醇、磷 脂酸、溶血磷脂等磷酯类脂质水平有关。

Objective To investigate the effect and mechanism of Gegen Qinlian Decoction （GQD） in ameliorating high-fat diet （HFD）-induced metabolic-associated fatty liver disease （MAFLD） in mice based on lipidomics. Methods Male SD rats were randomly divided into a modeling group （n=50） and a blank control group （n=10）. The blank control group was fed a standard diet，while the modeling group was fed a HFD. After 12 weeks，the successfully modeled rats were randomly divided into five groups （n=10 per group）：the model group，the positive drug group （rosiglitazone， 5 mg·kg -1 ），and the low-，medium-，and high-dose GQD groups （1.65，4.96，14.86 g·kg -1 ，respectively）. Except for the blank control group，all other groups continued HFD feeding. Concurrently，the respective treatments were administered by gavage （10 mL·kg -1 ） once daily for 16 consecutive weeks. Hepatic steatosis was observed by Oil Red O staining. Serum levels of total cholesterol （TC），triglycerides （TG），high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C），insulin （Fins），and fasting blood glucose （FBG） were measured，and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Liver lipidomics analysis was performed using UPLC-QTOF-MS technology to screen differential lipid metabolites and conduct metabolic pathway enrichment analysis. Results （1） Compared with the blank control group， the model group showed significantly increased body mass，HOMA-IR，FBG，and TG levels （P＜0.05，P＜0.01）. Hepatocytes were markedly swollen with prominent cytoplasmic fat vacuoles； lipid droplet fusion led to nuclear displacement or even disappearance. Diffusely distributed large and small lipid droplets were observed throughout the liver tissue， accompanied by significant inflammatory changes in hepatocytes. Compared with the model group， body mass and FBG levels were significantly reduced in the low- and medium-dose GQD groups （P＜0.05，P＜0.01）. TC and LDL-C levels were significantly decreased in the low- and high-dose GQD groups （P＜0.05， P＜0.01）. HOMA-IR was significantly dexreased in the low-dose GQD group （P＜0.05），and TG levels were significantly reduced in the medium-dose GQD group （P＜0.05）. All GQD treatment groups showed a marked reduction in the number and area of diffusely distributed lipid droplets within the liver tissue. （2） Sixteen potential lipid metabolic biomarkers of GQD intervention in MAFLD rats were identified. GQD increased the levels of phospholipids such as PC[22∶6（4Z，7Z，11E，13Z，15E，19Z）-2OH （10S，17）/14∶1（9Z）]，PS[20∶3（8Z，11Z，14Z）/LTE4]，and PA[20∶4（5Z，7E，11Z，14Z）-OH（9）/i-17∶0] in the liver tissue of MAFLD rats，while it decreased the levels of lipid metabolites such as Cer（d16∶1/16∶0） and LysoPC[18∶4（6Z，9Z， 12Z，15Z）/0∶0]. The differential lipid metabolites were primarily enriched in four metabolic pathways：glycerophospholipid metabolism，sphingolipid metabolism，inositol phosphate metabolism，and glycosylphosphatidylinositol （GPI）-anchor biosynthesis. Conclusion Gegen Qinlian Decoction can significantly ameliorate hepatic steatosis，serum lipid metabolic disorders，and insulin resistance in MAFLD rats. Its mechanism may be related to the regulation of glycerophospholipid metabolism and sphingolipid metabolism pathways， thereby improving the levels of phospholipids such as phosphatidylcholines，phosphatidylinositols，phosphatidic acids，and lysophosphatidylcholines in the liver.

R285.5

江西省教育厅科研项目（GJJ211237）；江西中医药大学校级创新团队发展计划项目（CXTD22015）。