关键词: 松果菊苷, 磷脂酰肌醇3激酶/蛋白激酶B通路, 乙型肝炎, 肝损伤, 免疫

Abstract: Objective To investigate the effect of Echinacoside (Ech) on liver injury in hepatitis B rats. Methods SD rats were divided into control group, Hepatitis B (HBV, 5 mL/kg HBV virus was injected into the tail vein twice a week for 3 consecutive weeks), low (Ech-L) and high (Ech-H) doses of Ech were injected into the stomach for HBV (8.33 and 33.32 mg/kg, respectively), HBV group was treated with positive drugs (lamivudine, 10 mg/kg) and Ech-H+BKM120 (40 mg/kg BKM120), with 12 animals in each group. The drug was administered once a day for 8 weeks. The activity of ALT and AST in serum of were detected. Serum level of gamma-interferon (IFN-γ) and interleukin (IL-4) was detected by ELISA; Flow cytometry was applied to detect Th1/Th2 in peripheral blood; Chromatin immunoprecipitation was applied to detect HBV DNA expression in liver tissue; HE staining was used to detect the pathological changes of liver tissue and score the damage; Western blot was applied to detect phosphorylated phosphatidylinositol 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT) proteins in liver tissue. Results Compared with the control group, hepatocytes in the hepatitis B group were swollen,nuclear staining was excessive, hepatic lobular structure was disorganized, pathological injury score, serum AST, ALT activity, IL-4 level, peripheral blood Th2, HBV DNA expression in liver tissue were all increased. Serum IFN-γ level, Th1, Th1/Th2 in peripheral blood, p-PI3K and p-AKT protein in liver tissue were all decreased (P＜0.05); Treatment with Ech-L, Ech-H and lamivudine reduced the swelling of HBV rat hepatocytes, cleared the structure of some liver cords, reduced pathological injury score, the activity of AST, ALT and IL-4 levels in serum, Th2 in peripheral blood and HBV DNA in liver tissue; The level of serum IFN-γ, Th1, Th1/Th2 in peripheral blood, and protein expression p-PI3K and p-AKT protein in liver tissue were increased (P＜0.05). BKM120 attenuated the ameliorative effect of high-dose Ech on hepatitis B-induced liver injury in rats. Conclusions Ech ameliorates liver injury in rats with hepatitis B, and the mechanism may be related to the activation of the PI3K/AKT pathway.

Key words: echinacoside, phosphatidylinositol-3 kinase/protein kinase B pathway, hepatitis B, liver injury, immune