Antifibrotic mechanism of action based on the corresponding on Traditional Chinese Medicine formula-syndrome to explore Yin-Chen-Hao Decoction regulation of Kupffer cell function and MAPK pathways

作者：Cao Hongyan; Bian Yanqin; Wu Chao; Li Jianyuan; Liu Ping; Sun Mingyu

来源：世界中医药, 2015, (2).

DOI：10.3969/j.issn.1673-7202(sj).2015.02.005

• Corresponding on Traditional Chinese medicine formula-syndrome
• Hepatic fibrosis
• Yin-Chen-hao Decoction
• &lsquo
• Er-ror free repair&rsquo
• principle
• Gene analysis

Objective:Our previous study showed significantly efficacy of series formula of Yin-chen-hao Decoction (YCHD)on fibrosis models in rats induced dimethynitrosamine (DMN).From the perspective of formula-efficacy-syndrome,we proposed a hy-pothesis ‘corresponding permit on formula-syndrome,gene regulation of formula on suffering body follow‘error free repair’princi-ple’and explore the mechanism of action of YCHD.Methods:Liver fibrosis was induced in rats with DMN.YCHD was adminis-trated intragastrically for 2 weeks for rats.At the end of the fourth week,all of the animals were sacrificed and their liver samples were collected for histology and gene chip analyses.Results:Compared with the normal group,the blood serum ALT level of the rats was remarkably increased (P <0.01 )four weeks after modeling;the inflammatory cells of hepatic tissue was remarkably infil-trated according to pathological observance,the deposition of collagen was remarkable (P <0.01 ).There were remarkable up-reg-ulation of the expression of the genes including Interleukin 1 beta (IL-1 b),Cd68,Tumor necrosis factor receptor superfamily, member 1 4 (Tnfrsf1 4),Tumor necrosis factor receptor superfamily,member 9 (Tnfrsf9),Fas,Cd1 4,Connective tissue growth factor (Ctgf),Collagen,type I,alpha 2(Col1 a2),Insulin-like growth factor binding protein,acid labile subunit(Igfals),Insu-lin-like growth factor 1 (Igf1 ),Insulin-like growth factor binding protein 1 (Igfbp1 ),Matrix metallopeptidase 1 2(Mmp1 2),Matrix metallopeptidase 2(Mmp2),Matrix metallopeptidase 23(Mmp23),Chemokine ligand 21 (Ccl21 )and Protein kinase C,beta (Prkcb)in hepatic tissue,and mitogen-activated protein kinase (MAPK)pathway was activated.Yin-Chen-Hao Decoction signif-icantly reduced the level of blood serum ALT inducted by DMN,restrained the infiltration and necrosis of the inflammatory cells of hepatic tissue,inhibited collagen deposit,decreased the expression of the genes including IL-1 b,Cd68,Tnfrsf1 4,Tnfrsf9,Fas, Cd1 4,Ctgf,Col1 a2,Igfals,Igf1 ,Igfbp1 ,Mmp1 2,Mmp2,Mmp23,Ccl21 and Prkcb,and restrained the activation of MAPK pathway.Conclusion:The hypothesis ‘corresponding permit on formula-syndrome,gene regulation of formula on suffering body follow‘error free repair’principle’was verified.The MOA of anti-fibrotic of Yin-Chen-Hao Decoction was regulation of the KCs action and MAPK pathway.

• 单位
  上海中医药大学