天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (10): 1810-1821.doi: 10.16333/j.1001-6880.2025.10.003 cstr: 32307.14.1001-6880.2025.10.003

• 研究论文 • 上一篇    下一篇

甘草干预马钱子总生物碱所致肝损伤大鼠的肝脏代谢组学研究

付晓艳1，巩子汉2，连小龙3，杨必乾1，殷亭湄1，高广淼1，邓  毅1,4*，杨秀娟1,4*   

  1. 1甘肃中医药大学，兰州 730000；2宁夏回族自治区中医医院暨中医研究院，银川 750021；3青海大学，西宁 810000；4甘肃中医药大学 中药药理与毒理学重点实验室，兰州 730000
  • 出版日期:2025-10-31 发布日期:2025-10-30
  • 基金资助:
    国家自然科学基金(81960723)；宁夏回族自治区重点研发计划(2022BEG03146)；甘肃省自然基金科技计划(25JRRA252)；甘肃省中药炮制技术传承基地项目(2022-13)

Protective effect of Glycyrrhizae Radix et Rhizoma on liver injury induced by total alkaloid of Strychni Semen in rats based on metabolomics

FU Xiao-yan1,GONG Zi-han2,LIAN Xiao-long3,YANG Bi-qian1,YIN Ting-mei1,GAO Guang-miao1,DENG Yi1,4*,YANG Xiu-juan1,4*   

  1. 1Gansu University of Chinese Medicine,Lanzhou 730000,China;2Research Institute,Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine,Yinchuan 750021,China;3Qinghai University,Xining 810000,China;4Key Laboratory of Pharmacology and Toxicology of Traditional Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China
  • Online:2025-10-31 Published:2025-10-30

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摘要：

探讨甘草对马钱子总生物碱所致肝损伤模型大鼠的保护作用及其机制。以马钱子总生物碱建立肝损伤大鼠模型，观察肝组织病理变化，检测肝功能、氧化应激、炎症因子及凋亡相关蛋白表达水平，同时采用非靶向代谢组学分析相关差异代谢物及代谢途径。与空白对照组比较，模型组大鼠肝组织出现中央静脉和肝窦严重充血、胞核固缩、炎症浸润等病理表现；血清丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）及肝组织中丙二醛（malondialdehyde，MDA）与促炎因子水平显著升高（P < 0.01）；超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase GSH-Px）水平显著降低（P < 0.01）；Western blot结果表明，肝组织中B淋巴细胞瘤-2（B-cell lymphoma-2，BCL-2）/BCL-2相关X蛋白（BCL-2-associated X protein，BAX）的蛋白表达显著降低（P < 0.05），而Caspase-3蛋白表达显著升高（P < 0.01）。与模型组比较，各给药组大鼠肝脏病理损伤明显改善；血清中ALT、AST及肝组织中MDA、炎症因子含量均显著降低，SOD、GSH-Px含量则显著升高（P < 0.01或P < 0.05）；BCL-2/BAX蛋白表达水平显著升高，Caspase-3蛋白表达显著降低（P < 0.05）。代谢组学分析表明，甘草高剂量组可显著回调11个差异代谢物，可富集3条代谢通路，其中色氨酸代谢最为显著。综上，甘草可通过抑制炎症因子水平、拮抗氧化应激、调控凋亡蛋白表达及色氨酸代谢，从而缓解马钱子总生物碱所致大鼠肝损伤。

关键词: 马钱子, 药物性肝损伤, 甘草, 炎症, BCL-2/BAX信号通路, 代谢组学

Abstract:

This study aims to explore the protective effect and mechanism of Glycyrrhizae Radix et Rhizoma on liver injury induced by total alkaloid of Strychni Semen. The liver injury model was induced by total alkaloid of Strychni Semen. Histopathological morphology, liver function, oxidative stress, inflammatory factors and the expression levels of apoptosis-related proteins were evaluated. Additionally, non-targeted metabolomics was utilized to analyze the differential metabolites and metabolic pathways. Compared with the blank control group, the model group showed severe hepatic congestion, nuclear pyknosis, and inflammatory infiltration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA), pro-inflammatory factors in liver tissues were significantly elevated (P < 0.01). In contrast, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly decreased (P < 0.01). Western blot results showed that the protein expression levels of B-cell lymphoma-2 (BCL-2)/BCL-2-associated X protein (BAX) in liver tissues were significantly reduced (P < 0.05), while the expression level of Caspase-3 protein was significantly increased (P < 0.01). Compared with the model group, Glycyrrhizae Radix et Rhizoma treatment groups showed a marked improvement in hepatic pathological damage. The levels of ALT, AST, MDA and inflammatory factors were reduced to varying degrees. Meanwhile, the levels of SOD and GSH-Px were significantly increased (P < 0.01 or P < 0.05). Additionally, the protein expression of BCL-2/BAX was significantly upregulated, while Caspase-3 expression was significantly downregulated (P < 0.05). Metabolomics analysis revealed that the high-dose Glycyrrhizae Radix et Rhizoma group significantly reversed 11 differential metabolites and enriched 3 metabolic pathways, with tryptophan metabolism being the most prominent. In conclusion, Glycyrrhizae Radix et Rhizoma alleviates liver injury in rats induced by total alkaloids of Strychni Semen by suppressing inflammatory factors, counteracting oxidative stress, regulating apoptosis-related protein expression, and modulating tryptophan metabolism.

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中图分类号:  R285.5 R965.2

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