Exploring The Mechanism Of Action Of “Red Peony Root-Aconite Powder” In The Intervention Of Rats With Acute-on-chronic Liver Failure Based On PI3K/AKT Signaling Pathwa

Objective: To investigate the protective effect of Radix Paeoniae Rubra and Radix Aconiti Lateralis on rats with chronic acute liver failure and its effect on the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods: ACLF rat models were prepared and divided into model group,positive group,Radix Paeoniae Rubra group,Radix Aconiti Lateralis group,Radix Paeoniae Rubra and Radix Aconiti Lateralis group,and blank group.After one week of intervention with corresponding drugs,liver function was detected by biochemical method,PT was detected by automatic hemagglutination analyzer,and IL-1β、IL-6、TNF-α was detected by ELISA,The expression of p-PI3 K,p-AKT(Ser473),the molecular markers of PI3K-Akt signaling pathway,was detected by Western blot;The expression of PI3 K and AKT m RNA was detected by real-time fluorescent quantitative PCR.Results:1.Liver function and coagulation function: Compared with blank group,the serum ALT,AST,TBIL and TBA levels in model group were significantly increased(P<0.05),while PT was significantly prolonged(P<0.05);Compared with model group,ALT,AST,TBIL and TBA levels in all intervention groups were decreased(P<0.05),and PT levels were significantly shortened(P<0.05),and the decrease was most significant in Red peony root and tablet group.2.Levels of inflammatory cytokines: Compared with blank group,the levels of IL-1β,IL-6 and TNF-α in model group were significantly increased(P<0.05),while the levels of IL-1β,IL-6 and TNF-α in all intervention groups were decreased compared with model group(P<0.05),and the decrease was most significant in Red paeonia-Fu tablet group.3.Liver histopathology: HE staining of liver tissue showed morphological changes of liver cells in the model group,including fusion necrosis,spotty or focal necrosis,fibrous tissue hyperplasia,and a large number of inflammatory cells infiltration in the portal area.4.Protein expression of P-PI3 K and P-Akt(Ser473): Compared with blank group,the protein expression levels of P-PI3 K and P-Akt in model group were significantly decreased(P<0.05),while the protein expression levels of P-PI3 K and P-Akt in intervention groups were significantly increased(P<0.05),among which the highest expression levels were found in Red peony root-Fu tablet group.5.PI3Km RNA and AKTm RNA levels: Compared with blank group,PI3 K and AKTm RNA expression levels of rats in model group were significantly decreased(P<0.05),while those of rats in intervention groups were significantly increased(P<0.05),and the highest expression levels were found in Red peony root-Fu tablet group.Conclusion:Radix Paeoniae Rubra and Radix Aconiti Lateralis may regulate the expression of related inflammatory factors by regulating the PI3K/AKT signaling pathway to reduce the immune inflammatory response in rats with chronic acute liver failure,thereby exerting a protective effect on the liver.