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AMPK activator down-regulates the expression of tissue factor in fulminant hepatitis mice

DAI Jie, LIN Ling, ZHOU Dan, AI Qing, GE Pu, ZHANG Li

Hospital of Chongqing University of Arts and Sciences, Chongqing 402160, China； Department of Pathophysiology； 3Department of Physiology； 4Laboratory of Stem cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China

Abstract

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.

Key words: AMP activated protein kinase; tissue factor ; coagulation ; fulminant hepatitis ; inflammation

Received: 2015-07-28　　Accepted: 2015-10-08

Corresponding author: 张力　　E-mail:

Citing This Article：

DAI Jie, LIN Ling, ZHOU Dan, AI Qing, GE Pu, ZHANG Li. AMPK activator down-regulates the expression of tissue factor in fulminant hepatitis mice. Acta Physiol Sin 2016; 68 (1): 35-40 (in Chinese with English abstract).