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目的:探讨梓醇对非酒精性脂肪肝病(non-alcoholic fatty liver disease, NAFLD)治疗及降脂机制。方法:高脂饮食喂养ICR小鼠8周以建立NAFLD体内模型，给予低剂量(50 mg/kg)、中剂量(150 mg/kg)、高剂量(300 mg/kg)剂量梓醇干预，分析小鼠体重、肝湿重、肝指数及生化指标。游离脂肪酸诱导人肝细胞LO2建立NAFLD细胞模型。实时荧光定量PCR检测脂肪酸合成相关基因水平。Western印迹法检测内质网应激(ERS)介导的蛋白激酶R样内质网激酶(PERK)-真核翻译起始因子2α(eIF2α)信号通路蛋白水平。结果:与模型小鼠相比，低剂量、中剂量、高剂量梓醇组小鼠体重[(39.43±1.84)g，(34.01±1.83)g，(32.28±1.11)g对(42.17±1.37)g，均n P<0.001]、肝湿重[(1.03±0.06)g，(0.79±0.05)g，(0.64±0.04)g对(1.30±0.13)g,n P<0.01或n P<0.001]、肝指数[(2.60±0.09)%，(2.32±0.09)%，(1.99±0.11)%对(3.07±0.30)%,n P<0.05或n P<0.001]降低。中、高剂量梓醇组模型小鼠总胆固醇、三酰甘油、低密度脂蛋白胆固醇、天冬氨酸转氨酶和丙氨酸转氨酶降低(n P<0.01或n P<0.001)，高密度脂蛋白胆固醇升高(n P<0.01或n P<0.001)。细胞模型中，脂肪酸合成基因及PERK-eIF2α通路蛋白水平的升高均被梓醇显著削弱(n P<0.05)，且这种削弱作用被信号通路激动剂逆转(n P<0.05)。n 结论:中药梓醇可能通过调控ERS介导的PERK-eIF2α信号通路发挥改善NAFLD的作用。“,”Objective:To investigate effect and underlying lipid-lowering mechanisms of catalpol in non-alcoholic fatty liver disease(NAFLD).Methods:In vivo model of NAFLD was established with high-fat diet-fed ICR mice for 8 weeks. Low(50 mg/kg), medium(150 mg/kg), and high(300 mg/kg) doses of catalpol were administered, and the body weight, liver weight, hepatic index, and biochemical parameters of the mice were analyzed. Free fatty acid-induced LO2 in human hepatocytes to establish NAFLD cell model. Quantitative realtime PCR reaction to detect fatty acid synthesis-related gene levels. Western blotting assay was adopted to analyze proteins in the endoplasmic reticulum stress(ERS)-mediated protein kinase RNA-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α) signaling pathway.n Results:Compared with model mice, body weight [(39.43±1.84)g, (34.01±1.83)g, (32.28±1.11)g n vs(42.17±1.37)g, all n P<0.001], liver weight [(1.03±0.06)g, (0.79±0.05)g, (0.64±0.04)gn vs(1.30±0.13)g, n P<0.01 orn P<0.001], and liver index [(2.60±0.09)%, (2.32±0.09)%, (1.99±0.11)%n vs(3.07±0.30)%, n P<0.05 orn P<0.001] were reduced in low, medium, and high doses of catapol model. Medium and high doses of catalpol diminished total cholesterol, triglyceride, low density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase(n P<0.01 orn P<0.001), increased high density lipoprotein-cholesterol(n P<0.01 orn P<0.001). In the cell model, elevated levels of both fatty acid synthesis genes and PERK-eIF2α pathway proteins were attenuated by catalase, and this attenuation was reversed by signaling pathway agonists.n Conclusion:The Chinese herb catalpol may play a role in improving NALFD by regulating the ERS-mediated PERK-eIF2α signaling pathway.