Dachengqi Decoction alleviate septic liver injury by regulating macrophage polarization through the JAK2/STAT3 pathway

The method applied in this paper were network pharmacology and animal experiment. Among them, network pharmacology was used to screen and predict the possible targets of Dachengqi Decoction and septic liver injury, and molecular docking and molecular dynamics were used to analyze the stability of the active components binding to JAK2. In animal experiment, 30 healthy male adult C57BL/6 mice were randomly divided into 6 groups: control group, model group, dexamethasone group (1.8 mg/kg), Dachengqi Decoction low (2.5 g/kg), medium (5 g/kg), and high (10 g/kg) concentration groups. The mice were given oral administration once a day. After 5 consecutive days of use, lipopolysaccharide was intraperitoneally injected (5mg/kg) was used to establish the model. The corresponding drugs were given orally 2 hours after model establishment, and the specimens were collected 6 hours later. HE staining was used to observe the pathological changes in the liver of mice; ELISA was used to detect IL-6, TNF-α, and IL-10 from serum and liver; liver function kit was used to detect ALT and AST from serum; Western blot was used to detect the protein expression of JAK2, p-JAK2, STAT3, p-STAT3, Arg-1, and iNOS in liver tissue; immunofluorescence was used to detect the protein expression of JAK2, STAT3, Arg-1, and iNOS; flow cytometry was used to detect the polarization of macrophages M1 and M2. The results of the above experiments show that, compared with the control group, the model group showed severe inflammatory reaction, liver tissue degeneration and inflammatory cell infiltration; Liver function ALT and AST were significantly increased (P<0.05); Pro-inflammatory factors IL-6, TNF-α were significantly increased, and anti- inflammatory factors IL-10 were increased (P<0.05); The protein expression of P-JAK2, P-STAT3 and iNOS in mouse liver tissue was significantly increased, and the protein expression of Arg-1 was significantly decreased (P<0.05); The proportion of M1 and M2 macrophages increased significantly (P<0.05). Compared with the model group, the liver injury of each drug intervention group was improved and the inflammatory response was reduced; Liver function ALT and AST were significantly reduced (P<0.05); Pro-inflammatory factors IL-6 and TNF-α decreased, and anti-inflammatory factors IL-10 increased (P<0.05); The protein expression of P-JAK2, P-STAT3, and iNOS decreased, and the protein expression of Arg-1 increased (P<0.05); The proportion of M1 macrophages decreased and the proportion of M2 macrophages increased (P<0.05). Moreover, the change trend of dexamethasone group and Dachengqi Decoction high concentration group was more obvious. Therefore, we can draw the conclusion that Dachengqi Decoction can alleviate liver injury caused by sepsis, and its mechanism is related to the regulation of JAK2/STAT3 pathway and the regulation of macrophage polarization.