4.6 Article

IκB kinase-beta inhibitor attenuates hepatic fibrosis in mice

期刊

WORLD JOURNAL OF GASTROENTEROLOGY
卷 17, 期 47, 页码 5203-5213

出版社

BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v17.i47.5203

关键词

Liver fibrosis; IKK2 inhibitor; Nuclear factor-kappa B; Tumor growth factor-beta1; Interleukin-6; Alpha-smooth muscle actin; C57BL mouse

资金

  1. Shanghai Municipal Health Bureau [2008Y032]

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AIM: To investigate the anti-fibrosis effect of I kappa B kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-kappa B (NF-kappa B), alpha-smooth muscle actin (alpha-SMA), tumor growth factor-beta1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), type. and type. collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-kappa B p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 +/- 9.77 mu/L vs 62.4 +/- 7.90 mu/L, P < 0.05) and aminotransferase (295.8 +/- 38.56 mu/L vs 212 +/- 25.10 mu/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 +/- 45.96 vs 77 +/- 7.79, P < 0.05), TGF-beta 1 (Western blotting 5.65% +/- 0.017% vs 2.73% +/- 0.005%, P < 0.05), TNF-alpha (11.58% +/- 0.0063% vs 8.86% +/- 0.0050%, P < 0.05), type. collagen (4.49% +/- 0.014% vs 1.90% +/- 0.0006%, P < 0.05) and type. collagen (3.46% +/- 0.008% vs 2.29% +/- 0.0035%, P < 0.05) as well as alpha-SMA (6.19 +/- 0.0036 mu/L vs 2.16 +/- 0.0023 mu/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-kappa B activation, which could become a remedial target for liver fibrosis. (C) 2011 Baishideng. All rights reserved.

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