天然产物研究与开发 ›› 2026, Vol. 38 ›› Issue (7): 1420-1427.doi: 10.16333/j.1001-6880.2026.7.004 cstr: 32307.14.1001-6880.2026.7.004

• 研究论文 • 上一篇    下一篇

多花黄精多糖通过激活AMPKα/SIRT1/PGC-1α信号通路改善酒精性肝损伤

刘  璇,杨  著,吕  圆,陈  妍,范欣欣,吴江平,吕秋月*   

  1. 安徽省多糖药物工程技术研究中心,皖南医科大学,芜湖 241002
  • 出版日期:2026-07-24 发布日期:2026-07-23
  • 基金资助:
    安徽省高等学校科学研究项目(自然科学类)重点项目(2024AH051923);皖南医科大学高层次人才科研启动经费项目(12060201168)

Polysaccharide from Polygonatum cyrtonema Hua ameliorates alcoholic liver injury by activating the AMPKα/SIRT1/PGC-1α signaling pathway

LIU Xuan,YANG Zhu,LYU Yuan,CHEN Yan,FAN Xin-xin,WU Jiang-ping,LYU Qiu-yue*   

  1. Anhui Provincial Center for Polysaccharide Drug Engineering and Technology,Wannan Medical University,Wuhu 241002,China
  • Online:2026-07-24 Published:2026-07-23

摘要:

探讨多花黄精多糖(Polygonatum cyrtonema Hua polysaccharide 1,PCP1)对酒精相关性肝病(alcohol-related liver disease,ALD)小鼠肝脏损伤的改善作用及其潜在机制,重点分析腺苷酸活化蛋白激酶α(adenosine 5'-monophosphate-activated protein kinase α,AMPKα)/沉默信息调节因子1(silent information regulator 1,SIRT1)/过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma coactivator-1 alpha,PGC-1α)信号通路的调节作用。采用慢性酒精喂养和急性酒精灌胃法建立ALD小鼠模型,随机分为对照组、模型组、阳性药组、PCP1低剂量组和PCP1高剂量组。通过HE染色、油红O染色及免疫组化评估肝脏病理变化,采用生化法检测血清天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)等肝功能指标,并使用ELISA测定肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)的水平。Western blot和免疫组化分析了AMPKα、SIRT1、PGC-1α等关键蛋白的表达。结果表明,PCP1显著改善酒精引起的肝脏病理损伤。HE染色和油红O染色显示,PCP1干预后,肝脏脂肪变性减轻,炎症浸润减少,肝细胞气球样变和坏死灶显著减少。血清学分析表明,PCP1显著降低ALT、AST、TC和TG水平,减少IL-6和TNF-α的分泌。PCP1还显著上调AMPKα/SIRT1/PGC-1α通路相关蛋白的表达。进一步实验表明,AMPKα抑制剂compound C显著减弱了PCP1的保护作用,表明PCP1的改善效果可能通过激活AMPKα/SIRT1/PGC-1α信号通路实现。综上所述,多花黄精多糖PCP1通过调节AMPKα/SIRT1/PGC-1α信号通路,改善酒精性肝损伤,为ALD提供了潜在的治疗策略。

关键词:

多花黄精多糖, 酒精相关性肝病, AMPKα/SIRT1/PGC-1α信号通路, 能量代谢

Abstract:

This study aims to investigate the ameliorative effects and underlying mechanisms of Polygonatum cyrtonema Hua polysaccharide 1 (PCP1) on alcohol-related liver disease (ALD) in mice, with a focus on analyzing the regulatory role of the adenosine 5'-monophosphate-activated protein kinase α (AMPKα)/silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling pathway. An ALD mouse model was established using chronic alcohol feeding and acute alcohol gavage, with mice randomly assigned to a control group, model group, positive drug group, PCP1 low-dose group, and PCP1 high-dose group. Liver pathological changes were evaluated through HE staining, oil red O staining, and immunohistochemistry. Biochemical methods were used to measure liver function indicators such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels, while ELISA was employed to determine the levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was used to analyze the expression of key proteins such as AMPKα, SIRT1, and PGC-1α. The results showed that PCP1 significantly ameliorated alcohol-induced liver damage. HE staining and oil red O staining revealed that PCP1 intervention reduced hepatic steatosis, inflammatory infiltration, hepatocyte ballooning, and necrotic foci. Serological analysis indicated that PCP1 significantly lowered ALT, AST, TC, and TG levels and reduced the secretion of IL-6 and TNF-α. PCP1 also significantly upregulated the expression of proteins related to the AMPKα/SIRT1/PGC-1α pathway. Additional experiments demonstrated that the AMPKα inhibitor compound C significantly attenuated the protective effects of PCP1, suggesting that PCP1's ameliorative effects may be achieved through activation of the AMPKα/SIRT1/PGC-1α signaling pathway. In conclusion, PCP1 improves alcoholic liver injury by regulating the AMPKα/SIRT1/PGC-1α signaling pathway, providing a potential therapeutic strategy for ALD.

Key words:

Polygonatum cyrtonema Hua polysaccharide 1, alcohol-related liver disease, AMPKα/SIRT1/PGC-1α signaling pathway, energy metabolism

中图分类号:  R285