一贯煎对M1型骨髓巨噬细胞治疗肝硬化大鼠模型效果的影响 及其机制分析.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD) on the efficacy of M1 bone marrowderived macrophages(M1-BMDMs) in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4. Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide. A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats. The rats for modeling were given subcutaneous injection of 50% CCl4 twice a week. Since week 7, the rats for modeling were randomly divided into model group(M group), YGJD group, M1-BMDM group, M1-BMDM+YGJD group, and sorafenib(SORA) group, and they were given subcutaneous injection of 30% CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF. CCR2 inhibitors were added to the drinking water, and each group was given the corresponding intervention. Related samples were collected at week 9. The rats were observed in terms of serum liver function parameters, liver pathology, hydroxyproline(Hyp) content in liver tissue, hepatic stellate cell activation, hepatic fibrosis and inflammation factors, and the expression levels of molecules associated with the Wnt signaling pathway. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the M group, the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin(TBil)（all P< 0.05)and a significant increase in the content of albumin(Alb)（P<0.05), and compared with the M1-BMDM group, the M1- BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05) and a significant increase in the serum level of Alb(P<0.05). Compared with the M1-BMDM group, the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α（P<0.05). Compared with the M1-BMDM group, the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05). As for the non-canonical Wnt signaling pathway molecules, compared with the M1-BMDM group, the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P< 0.05) and mRNA expression level of Fzd2（P<0.05), as well as significant reductions in the mRNA expression levels of Wnt4, Wnt5b, and Fzd3（P<0.05), while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin, LRP5, LRP6, Fzd5, and TCF. Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4, possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway, which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis. [ABSTRACT FROM AUTHOR]