天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (4): 563-569.doi: 10.16333/j.1001-6880.2021.4.004

• 研究论文 • 上一篇    下一篇

基于JNK通路研究老鹳草素对免疫性肝损伤小鼠的影响

李家妮,韩佳佳,程瑞华,赵唐莲,张可锋,饶聪矛,吴卫*,高雅*   

  1. 桂林医学院药学院,桂林 5410041
  • 出版日期:2021-04-28 发布日期:2021-05-10
  • 基金资助:
    广西壮族自治区教育厅八桂学者专项(桂财教函[2017]143号);国家自然科学基金(81760704)

Study on the effect of geraniin on immunological liver injury in mice based on JNK pathway

LI Jia-ni,HAN Jia-jia,CHENG Rui-hua,ZHAO Tang-lian,ZHANG Ke-feng,RAO Cong-mao,WU Wei*,GAO Ya*   

  1. College of Pharmacy,Guilin Medical University,Guilin 541004,China
  • Online:2021-04-28 Published:2021-05-10

摘要: 为探讨老鹳草素对脂多糖(LPS)所致小鼠免疫性肝损伤的保护作用及可能机制,60只小鼠被随机分为正常组、模型组、水飞蓟素组(180 mg/kg)和老鹳草素低、中、高剂量组(50、100、200 mg/kg),小鼠腹腔注射10 mg/kg的LPS诱导免疫性肝损伤。采取HE染色观察小鼠肝细胞病理改变情况;生化法检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性、碱性磷酸酶(ALP)、总胆红素(TBIL)水平,血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量;酶联免疫吸附试验(ELISA)法检测肝组织中炎症因子白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的含量;蛋白免疫印迹实验(Western blot)法检测小鼠肝组织中p-ASK1、ASK1、MKK4、p-MKK4、JNK、p-JNK、c-Jun和p-c-Jun的表达水平。结果表明,老鹳草素各剂量组和水飞蓟素组小鼠肝组织炎症坏死和凋亡现象有不同程度的减轻。与模型组相比,老鹳草素各剂量组可显著降低血清中的ALT、AST、ALP、TBIL、MDA和肝组织中IL-1β、TNF-α和IL-6水平,上调血清中SOD和GSH-Px的水平,并且抑制肝组织中p-ASK1、p-MKK4、p-JNK、p-c-Jun的表达。综上所述,老鹳草素对LPS诱导的免疫性肝损伤具有保护作用,其机制可能与抑制JNK通路相关。


关键词: 老鹳草素, 免疫性肝损, 脂多糖, 保肝, JNK信号通路

Abstract:

In order to explore the protective effect and possible mechanism of geraniin on immune liver injury induced by lipopolysaccharide (LPS) in mice,60 mice were randomly divided into normal group,model group and silymarin group (180 mg/kg) and geraniin low,medium and high dose groups (50,100,200 mg/kg).Mice were injected intraperitoneally with 10 mg/kg of LPS to induce immune liver injury.HE staining were used to observe the pathological changes of the livers;biochemical methods were used to detect serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) activities,alkaline phosphatase (ALP),total bilirubin (TBIL) levels,and serum superoxide biochemical dismutase (SOD),glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) content;enzyme-linked immunosorbent assay (ELISA) method for detection of interleukin-1β(IL-1β) in liver tissue,tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) content;Western blot method was used to detect p-ASK1,ASK1,MKK4,p-MKK4,JNK,p-JNK,c-Jun and p-c-Jun expression levels.The results showed that the inflammation,necrosis and apoptosis of the liver tissues of the mice in the geraniin group and the silymarin group were reduced to varying degrees.Compared with the model group,each dose group of geraniin can significantly reduce serum ALT,AST,ALP,TBIL,MDA and liver tissue IL-1β,TNF-α and IL-6 levels,up-regulate serum SOD and GSH-Px and inhibit the expression of p-ASK1,p-MKK4,p-JNK,p-c-Jun in liver tissue.In summary,geraniin has a protective effect on LPS-induced immune liver injury,and its mechanism may be related to the inhibition of the JNK pathway.

Key words: geraniin, immune liver damage, lipopolysaccharide, liver protection, JNK signaling pathway

中图分类号:  R965.1