期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 23, 期 21, 页码 3839-3849出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v23.i21.3839
关键词
Oxymatrine; Acute liver failure; Toll-like receptor 4; Apoptosis
资金
- Jiangsu Bureau of Traditional Chinese Medicine [YB2015177]
AIM To evaluate the effect of oxymatrine (OMT) on hepatocyte apoptosis in rats with lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF). METHODS LPS/D-GalN was used to establish a model of ALF in rats. To evaluate the effect of OMT, we assessed apoptosis by transmission electron microscopy, and the pathological changes in the liver by light microscopy with hematoxylin and eosin staining. An automated biochemical analyzer was used to measure serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Enzyme-linked immunosorbent assay was used to determine the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. Western blotting was used to detect protein levels in liver tissues. Streptavidin peroxidase immunohistochemistry was used to observe expression of Toll-like receptor (TLR) 4, active caspase-3, Bax and Bcl-2. RESULTS All rats in the normal control and OMT-pretreated groups survived. The mortality rate in the model group was 30%. OMT preconditioning down-regulated apoptosis of hepatocytes and ameliorated pathological changes in liver tissue. The levels of AST, ALT, TNF-a and IL-1 beta in the model group increased significantly, and were significantly reduced by OMT pretreatment. OMT pretreatment down-regulated expression of TLR4 and active caspase-3 and the Bax/Bcl-2 ratio, and upregulated expression of P-Akt(Ser473) (Akt phosphorylated at serine 473) and P-GSK3 beta(Ser9) (glycogen synthase kinase 3 beta phosphorylated at serine 9) induced by LPS/D-GalN. CONCLUSION OMT inhibits hepatocyte apoptosis by suppressing the TLR4/PI3K/Akt/GSK-3 beta signaling pathway, which suggests that OMT is an effective candidate for ameliorating acute liver failure.
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