Protective Effect and Mechanism of Buzhong Yiqitang on Concanavalin A-induced Acute Liver Failure in Mice / 中国实验方剂学杂志

ABSTRACT

<b>Objective:To explore the hepatoprotective effect and the mechanism of Buzhong Yiqitang (BZYQT) on mice with acute liver failure induced by Concanavalin A (ConA). <b>Method:A total of 80 mice were randomly divided into normal group, model group, Cyclosporine A (CsA) group, BZYQT low and high dose group (10.5, 21 g·kg^-1), 16 mice per group. All the mice except for normal group were injected intravenously with 15 mg·kg^-1 ConA. The treatment group mice were orally administrated with BZYQT, or intravenously administrated with 50 mg·kg^-1 CsA 30 min post ConA injection, normal and model group mice were orally administrated with ddH₂O at the same time. Blood, liver and spleen were collected 3 and 10 h post ConA injection. Cytokine levels of tumor necrosis factor alpha (TNF-<italic>α</italic>), interleukin-6 (IL-6), interleukin-12 (IL-12), interferon-gamma (IFN-<italic>γ</italic>) and monocyte chemoattractant protein-1 (MCP-1) in the serum were detected with cytometric bead array. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum were analyzed with fully automatic biochemical analyzer. The pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The activation of splenic CD4⁺ T lymphocytes was analyzed by flow cytometry. The expression and phosphorylation of extracellular regulated protein kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Western blot. <b>Result:Compared with normal group, model group showed higher levels of ALT and AST in the serum (<italic>P</italic><0.01), obvious pathological damage of liver tissue, higher levels of TNF-<italic>α</italic>, IL-6, IL-12, IFN-<italic>γ</italic> and MCP-1 in the serum (<italic>P</italic><0.01), higher expression of IL-2, IFN-<italic>γ</italic> and IL-4 CD4⁺ T lymphocytes in the spleen (<italic>P</italic><0.01), and elevated levels of phosphorylation of ERK1/2 and p38 MAPK (<italic>P</italic><0.01). Compared with the model group, BZYQT high dose group showed decreased levels of ALT and AST (<italic>P</italic>< 0.05, <italic>P</italic><0.01), reduced liver injury, decreased levels of TNF-<italic>α</italic>, IL-6, IL-12, IFN-<italic>γ</italic> and MCP-1 in the serum (<italic>P</italic><0.05, <italic>P</italic><0.01), reduced level of IL-2 and IFN-<italic>γ</italic> CD4⁺ T lymphocytes in the spleen (<italic>P</italic><0.05, <italic>P</italic><0.01), and reduced levels of phosphorylation of ERK1/2 and p38 MAPK (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion:BZYQT has a protective effect on mice with acute liver failure induced by ConA. The mechanism may be through inhibiting ERK1/2 and p38 MAPK signaling pathways, thereby reducing T lymphocyte activation and inflammatory cytokine secretion.