天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (11): 1890-1897.doi: 10.16333/j.1001-6880.2018.11.007

所属专题: No.2

• 研究论文 • 上一篇    下一篇

田基黄提取物抗CCl4诱导大鼠肝纤维化的作用及其机制研究

马冬梅1,高雅1,郭丹1,李家妮1,张可锋1,2*,段小群1*   

  1. 1桂林医学院,桂林 541004;2甘肃中医药大学,兰州 730000
  • 出版日期:2018-12-03 发布日期:2018-12-03
  • 基金资助:

    广西八桂学者专项(桂财教函[2017]143号)

The Protective Effect and Mechanism of Extracts of Hypericum Japonicum Thunb on Hepatic Fibrosis Rats Induced by Carbon Tetrachloride  

MA Dong-mei1, GAO Ya1, GUO Dan1, LI Jia-ni1, ZHANG Ke-feng1,2*, DUAN Xiao-qun1*   

  1. 1Guilin Medical University,Guilin 541004,China; 2Gansu University of Chinese Medicine,Lanzhou 730000,China
  • Online:2018-12-03 Published:2018-12-03

摘要: 探讨田基黄提取物(HJT)抗四氯化碳(CCl4)诱导的大鼠肝纤维化(HF)的作用及其机制。将60只雄性SD大鼠随机分为正常组、模型组、秋水仙碱(0.12 mg/kg)组和HJT(16 000、8 000、4 000 mg/kg)剂量组,每组10只。除正常组外,其余各组大鼠均腹腔注射40%的CCl4橄榄油溶液(1 mL/kg),2次/周,建立HF模型;同时各给药组灌胃相应剂量药物,正常组和模型组给予等体积蒸馏水,连续6周。末次给药后,采用HE染色和Masson染色观察大鼠肝组织病理学改变;生化法检测血清中ALT、AST活性;生化法检测肝组织中SOD、GSH-PX活性和MDA含量;ELISA法检测血清中HA、LN、PC Ⅲ、Ⅳ-C含量;ELISA法检测肝组织IL-1β、IL-6和TNF-α的含量;Western blot法检测大鼠肝组织中TGF-β1和α-SMA表达水平。结果显示,HJT(16 000、8 000、4 000 mg/kg)剂量组和秋水仙碱组能显著降低HF大鼠血清中ALT、AST、HA、LN、PC-Ⅲ、Ⅳ-C活性或含量,降低肝组织MDA含量,增加SOD和GSH-PX活性,同时减少肝组织IL-1β、IL-6及TNF-α含量,抑制肝组织TGF-β1和α-SMA蛋白表达;病理组织切片结果显示:HJT各剂量组和秋水仙碱组大鼠肝组织炎症坏死和HF病变程度明显减轻。本研究结果表明,HJT对CCl4诱导的HF大鼠有显著保护作用,其机制可能与抗炎、抗氧化和抑制TGF-β1蛋白表达有关。

关键词: 田基黄, 肝纤维化, 四氯化碳, 抗炎, 抗氧化, TGF-&beta, 1

Abstract: The purpose was to explore the protective effect and mechanism of the extract fraction of the Hypericum japonicum Thunb (HJT) on hepatic fibrosis induced by carbon tetrachloride (CCl4) in rats.60 male rats were randomly divided into normal group,model group,colchicine (0.12 mg/kg) group and HJT (16 000,8 000,4 000 mg/kg,crude drug dose) groups,with 10 rats in each group.Except for the normal group,other rats were intraperitoneal injection of 40% CCl4 olive oil mixed solution (1 mL/kg) twice a week for 6 weeks.From the first day of modeling,each administration group was administered by gavage with the corresponding drugs for intervention.Normal group and model group were given the same volume of distilled water once a day.After the last administration,the eyeballs was removed for taking blood and liver tissues were collected.The pathological changes of liver were observed by hematoxylin-eosin staining (HE) and Masson staining.The serum levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),hyaluronic acid (HA),laminin (LN),procollagetype Ⅲ (PCⅢ) and collage type Ⅳ (Ⅳ-C) were detected by biochemical detection.The levels of superoxide dismutase (SOD),glutathione glutathione peroxidase (GSH-PX),malonaldehyde (MDA),interleukin-1β (IL-1β),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).Western blot was used to detect the protein expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA).The results showed that HJT (16 000,8 000,4 000 mg/kg) and colchicine could significantly reduce the activities or contents of ALT,AST,PC-Ⅲ,Ⅳ-C,reduce the level of MDA in liver tissue,increase the activities of SOD and GSH-PX,and reduce the secretions of IL-1β,IL-6 and TNF-α.The results of histological sections showed that the degree of inflammatory necrosis and hepatic fibrosis in liver of each HJT dose group and colchicine group were significantly reduced.The results of the study show that HJT has a significant protective effect on CCl4-induced hepatic fibrosis,and its mechanism may be related to anti-inflammation,anti-oxidation and inhibition of TGF-β1 protein expression.

Key words: Hypericum japonicum Thunb, hepatic fibrosis, carbon tetrachloride, anti-inflammator, antioxidant, TGF-β1

中图分类号: 

R285