小檗碱对高脂饮食小鼠肝脏脂质沉积的干预作用及其机制

摘要/Abstract

摘要： 目的探讨小檗碱(BBR)对高脂饮食(HFD)诱导非酒精性脂肪性肝病(NAFLD)小鼠肝脏脂质沉积的干预作用及机制。方法将21只雄性野生型 C57BL/6J小鼠随机分为HFD组、HFD+BBR组及正常对照组,HFD+BBR组给予12 周 BBR口服[200 mg/(kg·d)]干预,比较各组体质量、肝质量、血清甘油三酯(TG)水平,并进行组织病理学及脂质组学、肠道微生物组、粪便代谢组学分析。结果 BBR可显著改善小鼠肝脏脂肪变性:HFD+BBR 组体质量降低 8.42%(P<0.01),肝质量降低10.33%(P=0.027),血清TG下降 39.5%(P<0.001),肝脏脂质滴及 NAFLD活动评分均显著降低(P=0.03)。脂质组学证实,BBR可抑制甘油二酯(P=0.004)、TG蓄积(P=0.01),恢复磷脂稳态,使肝脏总脂质减少 13.9%(P<0.05)。肠道微生物组分析显示,BBR可重塑菌群结构(P=0.002)、拟杆菌属丰度 (P<0.001)。粪便代谢组学表明,BBR 使胍丁胺水平升高 (P=0.05),且其与拟杆菌属呈强正相关(r=0.681,P=0.001),与肝脏中性脂质呈负相关。结论 BBR可通过调节肠道微生物组促进胍丁胺生成,双向调控肝脏脂质代谢,改善 HFD 诱导的肝脏脂肪变性,微生物-代谢物-宿主轴可能是 BBR 治疗 NAFLD 的关键机制。

关键词: 非酒精性脂肪性肝病, 小檗碱, 胍丁胺, 肠道微生物组, 拟杆菌属

Abstract: Objective To explore the interventional effect and mechanism of berberine (BBR) on hepatic lipid accumulation in mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). Methods Twenty-one male wild-type C57BL/6J mice were randomly divided into an HFD group, an HFD+BBR group, and a normal control group. The HFD+BBR group received oral BBR intervention at a dose of 200 mg/(kg·d) for 12 weeks. Body weight, liver weight, and serum triglyceride levels were compared among the groups, and histopathological analysis, lipidomics, gut microbiome analysis, and fecal metabolomics analysis were performed. Results BBR significantly ameliorated hepatic steatosis in mice: the HFD+BBR group showed an 8.42% reduction in body weight (P<0.01), a 10.33% decrease in liver weight (P=0.027), a 39.5% decline in serum triglyceride levels (P<0.001), as well as marked reductions in hepatic lipid droplets and NAFLD Activity Score (P=0.03). Lipidomic analysis confirmed that BBR inhibited the accumulation of diacylglycerol (P=0.004) and triglyceride (P=0.01), restored phospholipid homeostasis, and reduced total hepatic lipids by 13.9% (P<0.05). Gut microbiome analysis revealed that BBR reshaped the gut microbial community structure (P=0.002), with a significant increase in the abundance of Bacteroides (P<0.001). Fecal metabolomic analysis demonstrated that BBR increased agmatine levels (P=0.05), and agmatine was strongly positively correlated with Bacteroides (r=0.681, P=0.001) while negatively correlated with hepatic neutral lipids. Conclusion BBR ameliorates HFD-induced hepatic steatosis by regulating the gut microbiome to promote agmatine production and bidirectionally modulating hepatic lipid metabolism, revealing that the microbiome-metabolite-host axis may serve as a key mechanism underlying the therapeutic effects of BBR in NAFLD.

Key words: Non-alcoholic fatty liver disease, Berberine , Agmatine, Gut microbiota, Bacteroides

胡静娴, 李静, 谢晓岚, 华倩, 蒋淼. 小檗碱对高脂饮食小鼠肝脏脂质沉积的干预作用及其机制[J]. 肝脏, 2026, 31(5): 704-710.

HU Jing-xian, LI Jing, XIE Xiao-lan, HUA Qian, JIANG Miao. Interventional effect and mechanism of berberine on hepatic lipid deposition in high-fat diet-fed mice[J]. Chinese Hepatolgy, 2026, 31(5): 704-710.

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