Abstract: Objective This paper aimed to investigate the effect of hypoxia-inducible factor 1α(HIF-1α) in the development of nonalcoholic steatohepatitis (NASH). Methods Thirty male 57BL/6J mice were randomly divided into control, high-fat diet and methionine-choline-deficient diet (MCD) group, and the NASH model was established. The liver tissues were obtained for histological examination and hypoxyprobe staining. The HIF-1α mRNA and protein expression were respectively detected by Real-time PCR and Western blotting. The hepatic stellate cells, JS-1, were obtained and divided into control, adenoviral vector-infected and HIF-1α ShRNA adenovirus-infected group. The MTT test was applied for cell living assay. The collagen type 1 (COL1) and type 3 (COL3), TNF-α, IL-1βand TGF-β1 mRNA levels were detected by Real-time PCR. Results The hypoxyprobe staining showed that the percentages of positive staining in the high-fat diet and MCD diet groups were85% and 78%, significantly higher than 7% in the control(P<0.05); the HIF-1α mRNA levels in the two groups were 2.1 fold and 1.6 fold higher than in the control (P<0.05), and the HIF-1α protein expression was also greatly intensified; the cell viability in the HIF-1α ShRNA adenovirus-infected group was only 37%(P<0.05) compared to in the control, and the COL1, COL3, TNF-α, IL-1β and TGF-β1 mRNA decreased greatly compared to in the control(P<0.05). Conclusion HIF-1α might facilitate development of NASH, while needs further investigation.

Key words: Nonalcoholic steatohepatitis, Hypoxia-inducible factor 1α, High-fat diet, Methionine-choline-deficient diet, Mice, JS-1 cells