关键词: 火炭母; 鼠伤寒沙门菌; 肝损伤; TANK结合激酶1; 干扰素调节因子3

Abstract: 【Objective】 This study was aimed to investigate the protective effects of Polygonum chinense L. (P.chinense,PCL) on the liver of mice infected with Salmonella Typhimurium (S. Typhimurium) and its underlying mechanism.【Method】 48 male BALB/c mice were randomly divided into 6 groups:Normal,model,positive drug,PCL-H,PCL-M and PCL-L groups.Mice in the positive drug group were given gentamicin (20 mg/kg) orally.Mice in the PCL-H,PCL-M and PCL-L groups were orally administered with PCL at 16,8 and 4 g/kg,respectively.The normal and model groups mice were given with the same volume of PBS.The drugs were administered for 8 consecutive days.After 2 days of prophylactic administration,the mice in the normal group were given 0.2 mL PBS,and the mice in the other groups were given 0.2 mL S. Typhimurium solution (5×10⁴ CFU/mL) at one time.After the administration,the mice were killed,and the liver was dissected to make tissue sections and stained with HE to observe the pathological changes of the liver.The liver tissue suspension was cultured in the plate medium to detect the bacterial load in the liver of the mice.Western blotting was used to detect the expression levels interferon alpha (IFN-α),interferon beta (IFN-β),interferon gamma (IFN-γ),tumor necrosis factor α (TNF-α),interleukin 1β (IL-1β),TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) protein.【Result】 The pathological observation of liver showed that the liver of mice in the model group had congestion and a large number of inflammatory cells infiltrated.The hepatocytes were obviously swollen and disordered,the cytoplasmic staining was deepened,and the hepatocytes were necrotic and apoptotic.In PCL-H mice,there were a few inflammatory cells in liver,congestion and necrosis and apoptosis of liver cells were improved.In PCL-M and PCL-L,except for hepatocytes with dark cytoplasmic staining,slight swelling,and disordered arrangement,other lesions were not obvious.Compared with the normal group,the load of S. Typhimurium in liver of the model group mice was significantly increased (P＜0.05),and the expressions of IRF3,P-IRF3,IFN-α,IFN-β and IFN-γ were significantly decreased (P＜0.05),the expressions of TNF-α and IL-1β were significantly increased (P＜0.05).Compared with the model group,the load of S. Typhimurium in liver of mice in PCL-H,PCL-M and PCL-L groups was significantly decreased (P＜0.05).Among them,PCL-M could significantly enhance the phosphorylation of TBK1 and IRF3 proteins and the expression of IRF3 protein (P＜0.05).The protein levels of IFN-α,IFN-β and IFN-γ were significantly increased (P＜0.05),and the secretions of TNF-α and IL-1β were significantly decreased (P＜0.05).【Conclusion】 PCL could induce the production of interferon through enhancing TBK1-IRF3 pathway to alleviate the liver damage of mice infected by S. Typhimurium,and the dosage of 8 g/kg was better.

Key words: Polygonum chinense L.; Salmonella Typhimurium; liver damage; TBK1; IRF3