天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (3): 386-393.doi: 10.16333/j.1001-6880.2021.3.005

所属专题: 抗肝损伤专题

• 研究论文 • 上一篇    下一篇

基于LIN28A/NF-κB信号通路研究狗肝菜多糖缓解肝纤维化的作用机制

郑董璇1,张可锋1,晋玲2,钟明利1,赵唐莲1,曹后康2,段小群1*,高雅1*   

  1. 1桂林医学院药学院,桂林 541004;2甘肃中医药大学药学院,兰州 730000

  • 出版日期:2021-03-28 发布日期:2021-04-01
  • 基金资助:
    国家自然科学基金(81760114,81960779);广西自然科学基金(2017GXNSFAA198218,2018GXNSFAA281040)

Study on the mechanism of polysaccharides from Dicliptera chinensis in alleviating liver fibrosis based on LIN28A/NF-κB signaling pathway

ZHENG Dong-xuan1,ZHANG Ke-feng1,JIN Ling2,ZHONG Ming-li1,ZHAO Tang-lian1,CAO Hou-kang2,DUAN Xiao-qun1*,GAO Ya1*#br#

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  1. 1Guilin Medical University,Guilin 541004,China; 2Gansu University of Traditional Chinese Medicine,Lanzhou 730000, China
  • Online:2021-03-28 Published:2021-04-01

摘要:

探讨狗肝菜多糖(DCP)通过LIN28A/NF-κB信号通路改善大鼠肝纤维化(HF)。将60只雄性SD大鼠以每组10只,随机分成正常组、模型组、秋水仙素组和DCP低中高剂量(50、100、200 mg/kg)组。通过每周进行腹腔注射40%的四氯化碳(CCl4)橄榄油溶液(1 mL/kg)2次,建立HF大鼠模型,正常组按照相同剂量注射橄榄油;每日根据体重给予秋水仙素组和DCP低中高剂量组大鼠相应的药物进行治疗,正常组与模型组大鼠按照相同计算方式灌胃蒸馏水,造模与治疗过程持续6周。实验终点,使用HE染色和Masson染色观察和评价大鼠肝脏组织病变程度;使用ELISA法检测大鼠血清中HA、LN、PC III、IV-C含量和肝脏组织中炎症因子(IL-1β、IL-6和TNF-α)水平;使用PCR和Western blot检测和分析大鼠肝脏组织中α-SMA、TGF-β1、LIN28A、NF-κBp65、MMP9、COX-2、iNOS的mRNA和蛋白表达水平。结果显示,秋水仙素和各剂量的DCP均可以降低大鼠血清中HA、LN、PC III和IV-C含量,且DCP高剂量组效果明显;病理结果显示,与模型组相比DCP组和秋水仙素组可以明显缓解大鼠肝脏的病变程度;肝脏组织中的α-SMA、TGF-β1、LIN28A、NF-κBp65、MMP9、COX-2和iNOS的表达均有不同程度的下降。综上所述,DCP对大鼠HF具有明显改善作用,其机制与抑制NF-κBp65蛋白表达,减少下游炎症因子的释放而发挥抗HF作用。

关键词: 狗肝菜多糖(DCP), 肝纤维化, CCl4, LIN28A/NF-κB信号通路

Abstract:

To study the effect of polysaccharide from Dicliptera chinensis (DCP) on LIN28A/NF-κB signaling pathway in liver fibrosis.Sixty male SD rats were randomly divided into normal group,model group,colchicine group and DCP low,medium and high dose (50,100 and 200 mg/kg) groups with 10 rats in each group.The liver fibrosis rat model was established by intraperitoneal injection of 40% CCl4 olive oil solution (1 mL/kg) twice a week.The normal group was injected with olive oil at the same dose.The rats in the colchicine group and the DCP low,medium and high dose group were given the corresponding drugs every day according to their body weight.The rats in the normal group and the model group were given distilled water according to the same calculation method.The modeling and treatment process lasted 6 weeks.At the end point of the experiment,HE staining and Masson staining were used to observe and evaluate the degree of liver tissue lesions in rats The levels of HA,LN,PC III,IV-C in serum and inflammatory factors (IL-1β,IL-6 and TNF-α) in liver tissue were detected by ELISA.The mRNA and protein expression levels of α-SMA,TGF-β1,LIN28A,NF-κBp65,MMP9,COX-2 and iNOS in rat liver tissue were detected and analyzed by PCR and Western blot.The results showed that the contents of HA,LN,PC III and IV-C in rat serum in colchicine and various doses of DCP groups,and the effect was obvious in DCP high dose group.The pathological results showed that the degree of liver lesions in DCP group and colchicine group were significantly relieved compared with that in model group.The expression of α-SMA,TGF-β1,LIN28A,NF-κBp65,MMP9,COX-2 and iNOS in liver tissue was decreased in different degrees.To sum up,DCP can obviously improve HF in rats,and its mechanism is related to the inhibition of NF-κB signaling pathway by DCP.

Key words: Dicliptera chinensis , polysaccharide (DCP), liver fibrosis, CCl4, LIN28A/NF-κB signal pathway

中图分类号:  R965.1