天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (8): 1497-1503.doi: 10.16333/j.1001-6880.2025.8.011 cstr: 32307.14.1001-6880.2025.8.011

• 开发研究 • 上一篇    下一篇

胡椒碱对小鼠急性酒精性肝损伤的保护作用及机制

姜新宇1†,李文涛2†,宁  宇3,袁浩铭3,王金红3*,孙善明1*   

  1. 1山东第二医科大学第一附属医院(潍坊市人民医院),潍坊 261041;2山东第二医科大学基础医学院;3山东第二医科大学药学院,潍坊 261053
  • 出版日期:2025-08-25 发布日期:2025-08-25
  • 基金资助:
    山东省自然科学基金(ZR2021QH095);潍坊医学院附属医院科技发展项目(2023FYZ002)

Protective effect and mechanism of piperine on acute alcoholic liver injury in mice

JIANG Xin-yu1†,LI Wen-tao2†,NING Yu3,YUAN Hao-ming3,WANG Jin-hong3*,SUN Shan-ming1*   

  1. 1Weifang People′s Hospital,Shandong Second Medical University,Weifang 261041,China;2School of Basic Medical Sciences,Shandong Second Medical University; 3School of Pharmacy,Shandong Second Medical University,Weifang 261053,China
  • Online:2025-08-25 Published:2025-08-25

摘要:

探讨植物荜茇活性成分之一胡椒碱(piperine,PIP)对小鼠急性酒精性肝损伤的保护作用及机制。雄性C57BL/6小鼠50只,随机分为5组:正常对照组、模型组、PIP低、中、高剂量组,每组10只。除正常对照组外,其余4组小鼠建立急性酒精性肝损伤模型。试剂盒测定小鼠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)、碱性磷酸酶(alkaline phosphatase,AKP)和肝脏组织丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、白细胞介素-6(interleukin-6,IL-6)、IL-1β、IL-18含量,HE染色和天狼星红染色观察肝脏形态,免疫荧光检测Kelch样ECH关联蛋白1(Kelch-like ECH-associated protein 1,Keap1)和核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,NRF2)表达,Western blot检测Keap1和NRF2蛋白表达。结果发现,PIP降低小鼠血清AST、ALT、TG、TC和AKP含量,降低肝脏IL-6、IL-1β、IL-18和MDA含量,升高SOD和GSH-Px含量(P < 0.05,P < 0.01)。PIP改善肝脏形态学异常,同时降低肝脏Keap1表达,增加NRF2表达(P < 0.05,P < 0.01)。综上所述,PIP对小鼠急性酒精性肝损伤具有保护作用,机制可能与抗氧化应激作用有关。

关键词: 胡椒碱, 急性酒精性肝损伤, 炎症反应, 氧化应激

Abstract:

The protective effect and mechanism of piperine (PIP), an active ingredient in plant Piper longum L., on acute alcoholic liver injury in mice were investigated. Fifty male C57BL/6 mice were randomly divided into five groups: normal control group, model group, low-dose, medium-dose and high-dose groups of PIP, with ten mice in each group. Except the normal control group, acute alcoholic liver injury model was established in the remaining mice. Reagent kits were used to detect the content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), alkaline phosphatase (AKP) in serum and malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), IL-1β, IL-18 in liver tissue. The liver morphology was observed by HE staining and Sirius red staining. The expression of Kelch like ECH-associated protein 1 (Keap1) and nuclear factor E2-related factor 2 (NRF2) was observed by immunofluorescence, and the expression of both proteins was detected by Western blot. The results showed that PIP reduced the levels of serum AST, ALT, TG, TC and AKP in mice, decreased the levels of liver IL-6, IL-1β, IL-18 and MDA, increased the levels of SOD and GSH-Px (P < 0.05, P < 0.01). PIP improved liver morphological abnormalities, reduced Keap1 expression and increased NRF2 expression in the liver (P < 0.05, P < 0.01). In conclusion, PIP can ameliorate the acute alcoholic liver injury in mice, and the mechanism may be related to antioxidant stress effect.

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中图分类号:  R575