Mechanism of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata herbal pair in promoting hepatocellular regeneration in chronic acute liver failure based on HGF/PI3K/Akt signaling axis
Based on the hepatocyte growth factor(HGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling axis,this study investigated the therapeutic effect of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata(PRR-ALRP)her-bal pair on acute-on-chronic liver failure(ACLF)rats and its impact on hepatocellular regeneration.The rat model of ACLF was con-structed by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of lipopolysaccharides(LPS)+D-galactosamine(D-GalN).The rats were divided into normal control(NC)group,model(vehicle)group,PRR-ALRP(5.85 g·kg-1)group,and hepatocyte growth factor granules(HGFG,4.05 g·kg-1)group.Hematoxylin-eosin(HE)staining was used to observe pathological changes in rat liver tissues.Serum alanine aminotransferase(ALT),aspartate transaminase(AST),and total bilirubin(TBIL)were detected using an automatic biochemical analyzer.The levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)inflammatory factors were detected by ELISA.Immunofluorescence staining was used to detect the positive expres-sion of proliferating cell nuclear antigen(PCNA),antigen identified by monoclonal antibody(Ki67),and cell cycle protein B1(Cy-clinB1).Real-time fluorescence-based quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of HGF,growth factor receptor-bound protein 1(Gabi),PI3K,Akt,phosphorylated PI3K(p-PI3K),and phosphorylated Akt(p-Akt).The results showed that compared with the vehicle group,the PRR-ALRP group had re-duced liver tissue pathological scores,improved liver function,and reduced inflammatory response,with enhanced PCNA,Ki67,and CyclinB1 fluorescence expression.Furthermore,compared with the model group,the PRR-ALRP group showed upregulated expression of HGF and Gab1 proteins,as well as activation of PI3K and Akt phosphorylation.These findings suggest that PRR-ALRP herbal pair exerts anti-liver failure effects by alleviating hepatocyte inflammatory damage and promoting hepatocellular regeneration,and its specific regulatory mechanism may be related to the activation of the HGF/PI3K/Akt signaling pathway.
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