thromboplastin and imidazolecarboxamide

AMP activated protein kinase (AMPK) is a pivotal metabolic regulatory enzyme and novel target of controlling inflammation. Our previous studies had demonstrated that 5-amino-4-imidazolecarboxamide riboside (AICAR), an AMPK activator, attenuated lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced fulminant hepatitis via suppressing inflammatory response. Since inflammation usually activates the coagulation response and aggravates inflammation-induced tissue injury, the present study was to explore the effects of AICAR on inflammation-induced activation of coagulation. Male BALB/c mice received LPS/D-gal intraperitoneal injection were used as fulminant hepatitis model. Western blot was used to detect tissue factor (TF) and hypoxia-inducible factor 1α (HIF-1α) protein expressions in hepatic tissue, as well as nuclear factor kappa B (NF-κB) p65 translocation into the nucleus. Real-time quantitative PCR was used to analyze erythropoietin (EPO) mRNA expression level. Lactic acid (LA) level in hepatic tissue was detected by kit. The results showed that LPS/D-gal induced the enhanced expression of TF, elevation of NF-κB p65 nuclear translocation, up-regulation of HIF-1α and EPO expressions, and increased LA level. These above alterations could be suppressed by AICAR. These results suggest that AICAR may down-regulate LPS/D-gal-induced TF expression (coagulation activity), and relieve hepatic hypoxia and metabolic disorder via suppressing the activity of NF-κB, which may be a novel mechanism of the beneficial effect of AICAR on LPS/D-gal-induced fulminant hepatitis.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Down-Regulation; Erythropoietin; Hepatitis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Lipopolysaccharides; Male; Mice; NF-kappa B; Thromboplastin; Up-Regulation