The inhibitory effect of ligustrazine combined with paeonol on rat liver fibrosis induced by CCl4 and mechanisms / 中国药理学通报

ABSTRACT

Aim To explore the inhibitory effect of li-gustrazine combined with paeonol on rat liver fibrosis induced by CCl4 and its mechanisms,so as to provide new treatment strategies for liver fibrosis in clinical. Methods Cleaning laboratory male SD rats were ran-domly divided into blank control group,model group (CCl4 ),ligustrazine group,paeonol group and combi-nation group (ligustrazine+paeonol).HE staining was used to observe the pathological change.Masson stai-ning and Sirius red staining was used to observe the collagen deposition.The levels of serum ALT,AST, ALP and hydroxyproline were detected by automatic bi-ochemistry analyzer.Western blot detected the markers of liver fibrosis.HSC-T6 cell was divided into model group,ligustrazine group,paeonol group and combina-tion group.The protein and gene expression of inflam-mation and apoptosis pathway was analyzed by Western blot and real time-PCR.Results Ligustrazine com-bined with paeonol could significantly improve liver tis-sue pathology changes caused by CCl4 .It could reduce serum ALT, AST, ALP and hydroxyproline levels. Moreover,it could also inhibit liver fibrosis marker protein expression,and thus reduce the deposition of collagen fibers.The effect was better than that in sin-gle intervention group.Combination group could inhib-it the inflammatory pathways related protein expression in HSC cells and promote the apoptosis of HSC cells. Conclusion Ligustrazine in combination with paeonol has significant anti-fibrosis effect,and the effect is bet-ter than both single intervention.The effect may be due to the interference with TNF-α/NF-κB pathway in the HSC cells,which promotes its apoptosis and inhib-its the generation of extracellular matrix.