Abstract:Objective: To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis. Method: In vivo experiments were conducted on a rat model of liver cirrhosis induced by carbon tetrachloride. Normal group, model group, colchicine group, and low, medium, and high dose groups of Jiawei Jisheng Shenqi Decoction were set up. HE staining and Masson staining were used to observe the pathological changes in liver tissue of rats in each group;Test kit was used to to detect changes in serum liver function in each group of rats; Elisa was used to detect the levels of hyaluronic acid (HA), laminin (LN), procollagen III (PCIII)and collagen type IV(COL4) in each group of rats; Western blot was used to detect the expression of hypoxia inducible factor-1α(HIF-1α), Notch1, Jagged1, and α-smooth muscle actin(α-SMA) proteins in rats. In vitro experiments were conducted on HSC-T6 cells, and the CCK-8 method was used to screen for the most suitable (100 μM, 200 μM, 400 μM, 600 μM, 800 μM) concentrations of CoCl2 cultured cells and the optimal intervention concentrations of drug containing serum (5%, 10%, 15%, 20%); Scratch test was used to detect the migration ability of cells in each group; Flow cytometry was used to detect changes in apoptosis rate of cells in each group; Western blot was used to detect the expression of HIF-1α, Notch1, Jagged1, a-SMA, Matrix Metallopeptidase 9(MMP9), and Tissue Inhibitor of Metalloproteinases 1(TIMP-1) proteins in each group of cells. Results:In vivo experiment: Compared with the control group, the model group rats showed significantly increased liver swelling, inflammatory cell infiltration, and collagen deposition, as well as the appearance of pseudolobules. The levels of serum ALT, AST, HA, LN, PCIII, COL4 were significantly increased, while ALB was significantly decreased. The expression of HIF-1α, Notch1, Jagged1, and α-SMA proteins in liver tissue was significantly increased (P<0.01). Compared with the model group, the liver swelling, inflammatory cell infiltration, and collagen deposition in each treatment group rats were significantly reduced, and the degree of fibrosis was reduced. The levels of serum ALT, AST, HA, LN, PCIII, COL4 were significantly decreased, while ALB was significantly increased. The expression of HIF-1α, Notch1, Jagged1, and α-SMA proteins in liver tissue was also significantly increased. Decreased to varying degrees (P<0.05). In vitro experiments: Hypoxia can promote HSC-T6 migration, reduce HSC-T6 apoptosis, and increase the expression of HIF-1α, Notch1, Jagged1, a-SMA, and TIMP-1 proteins, while reducing the expression of MMP9 protein (P<0.01). The serum containing Jiawei Jisheng Shenqi Decoction can inhibit HSC-T6 migration, promote HSC-T6 apoptosis, and lower the expression of HIF-1α, Notch1, Jagged1, a-SMA, and TIMP-1 proteins, while enhance the expression of MMP9 protein (P<0.01). However, its inhibitory effect on HSC-T6 cell activation can be reversed by the HIF-1 α agonist DMOG. Conclusion: Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment through the HIF-1α/Notch pathway, thereby exerting an anti liver cirrhosis effect.