摘要
AIM: To investigate the anti-fibrosis effect of IκB 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-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/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-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/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-κB activation, which could become a remedial target for liver fibrosis.
AIM： To investigate the anti-fibrosis effect of IκB 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-κB （NF-κB）, alpha-smooth muscle actin （α-SMA）, tumor growth factor-beta1 （TGF-β1）, tumor necrosis factor-alpha （TNF-α）, typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS： A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase （103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P 〈 0.05） and aminotransferase （295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/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-β1 （Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P 〈 0.05）, TNF-α （11.58% ± 0.0063% vs 8.86% ± 0.0050%, P 〈 0.05）, typeⅠcollagen （4.49% ± 0.014% vs 1.90% ± 0.0006%, P 〈 0.05） and type Ⅲ collagen （3.46% ± 0.008% vs 2.29% ± 0.0035%, P 〈 0.05） as well as α-SMA （6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/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-κB activation, which could become a remedial target for liver fibrosis.
基金
Supported by Shanghai Municipal Health Bureau Youth Grant, No. 2008Y032
