中国药物警戒 ›› 2025, Vol. 22 ›› Issue (12): 1352-1359.
DOI: 10.19803/j.1672-8629.20250639

• 基础与临床研究 • 上一篇    下一篇

红曲地龙片的预防性降血脂效应及代谢调控研究

李高芾1, 王宁宁1, 孙悦2, 夏天天3, 周维1,2#, 高月1,3,4*   

  1. 1军事科学院军事医学研究院,北京 100850;
    2青海大学药学院,青海 西宁 810000;
    3青海大学医学院中医系,青海 西宁 810000;
    4中国人民解放军总医院肾脏疾病国家重点实验室,北京 100853
  • 收稿日期:2025-09-09 发布日期:2025-12-19
  • 通讯作者: *高月,女,博士,中国工程院院士,中药药理与毒理研究。E-mail: gaoyue@bmi.ac.cn;#为共同通信作者。
  • 作者简介:李高芾,女,在读博士,药学。
  • 基金资助:
    国家重点研发计划(2025YFC3507500)

Preventive Hypolipidemic Effect of Hongqu Dilong Tablets and Metabolic Regulation

LI Gaofu1, WANG Ningning1, SUN Yue2, XIA Tiantian3, ZHOU Wei1,2#, GAO Yue1,3 4*   

  1. 1Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China;
    2School of Pharmacy, Qinghai University, Xining Qinghai 810000, China;
    3Department of Traditional Chinese Medicine, School of Medicine, Qinghai University, Xining Qinghai 810000, China;
    4State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
  • Received:2025-09-09 Published:2025-12-19

摘要: 目的 探究红曲地龙片的降血脂效应及代谢调控作用,为此类药物后续作用机制研究及临床安全用药提供参考。方法 建立高脂饮食C57BL/6N小鼠模型,雌雄各18只,使用0.208 mg·g-1红曲地龙片连续灌胃给药1个月,比较小鼠体重、血清丙氨酸氨基转移酶(ALT)与天冬氨酸氨基转移酶(AST)、血脂、血糖及肝脏病理切片的变化;基于血清代谢组学,探究红曲地龙片对小鼠代谢的调控作用,解析其可能的降血脂机制。结果 与高脂饮食模型组相比,红曲地龙片组雌鼠、雄鼠体重均显著降低,肝功能指标亦得到一定程度降低;红曲地龙片可显著逆转高脂饮食导致的雌鼠、雄鼠血清总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)升高,并可显著降低雄鼠血糖;肝组织苏木精-伊红(HE)染色和油红O染色提示红曲地龙片可显著降低雌、雄小鼠肝组织脂质累积,并恢复高脂饮食造成的肝细胞排列混乱、细胞间隙扩张等现象。代谢组学提示红曲地龙片通过调节脂质代谢及鞘脂信号通路,并影响氨基酸、蛋白质等物质代谢,发挥降脂效应。结论 红曲地龙片可有效逆转高脂饮食对雌鼠和雄鼠体重、血脂及肝脂质沉积的影响,其机制可能与调节脂质相关物质代谢网络有关。

关键词: 红曲米, 地龙, 血脂, 脂代谢, 肝脏, 代谢组, 小鼠

Abstract: Objective To investigate the preventive hypolipidemic effects and metabolic regulatory mechanisms of Hongqu Dilong tablets so as to provide a reference for subsequent research on the mechanism of action of such drugs and their safe clinical use. Methods A high-fat diet (HFD)-induced C57BL/6N mouse model was established. Mice, male or female, were orally administered Hongqu Dilong tablets (0.208 mg·g⁻¹) daily for 4 weeks. Body weight, serum levels of ALT, AST, blood lipids, glucose, and liver histopathology were assessed. Serum metabolomics was employed to explore metabolic alterations and potential mechanisms. Results Compared with the HFD model group, mice treated with Hongqu Dilong tablets had their body weight significantly reduced and liver function (ALT and AST) improved. The treatment markedly reversed HFD-induced elevations in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) while significantly reducing blood glucose levels in male mice. Histopathological examination (H&E and oil red O staining) revealed that the tablets alleviated hepatic lipid accumulation and mitigated HFD-induced structural abnormalities, including disorganized hepatocyte arrangement and expanded intercellular spaces. Metabolomic analysis suggested that the preventive hypolipidemic effects were mediated by regulating lipid metabolism and sphingolipid signaling pathways, along with modulations in amino acid and protein metabolism. Conclusion Hongqu Dilong tablets can effectively counteract HFD-induced increases in body weight, dyslipidemia, and hepatic lipid deposition in mice of both sexes. The mechanism may involve regulation of a metabolic network related to lipid metabolism.

Key words: Red Yeast Rice, Earthworms, Blood Lipids, Lipid Metabolism, Liver, Metabolomics, Mice

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