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 inject...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 展开更多
目的研究金雀异黄素(Gen)对类风湿关节炎(RA)患者间充质干细胞(MSCs)中的核因子κB受体活化因子(RANK)、核因子κB受体活化因子配体(RANKL)和骨保护素(OPG)系统的影响及其机制。方法分离培养正常人与RA患者的骨髓MSCs(BM-MSCs),分为空...目的研究金雀异黄素(Gen)对类风湿关节炎(RA)患者间充质干细胞(MSCs)中的核因子κB受体活化因子(RANK)、核因子κB受体活化因子配体(RANKL)和骨保护素(OPG)系统的影响及其机制。方法分离培养正常人与RA患者的骨髓MSCs(BM-MSCs),分为空白对照组、Gen处理组、雌二醇(E_2)处理组和Gen+雌激素受体拮抗剂(ICI182780)组,采用Western blot法检测BM-MSCs中RANK、RANKL、OPG的表达;采用免疫荧光法检测雌激素受体α(ERα)细胞内分布情况。结果 Western blot结果显示:与正常人BM-MSCs相比,RA患者BM-MSCs中的RANK的蛋白表达水平明显升高,OPG的蛋白表达水平明显降低,RANKL/OPG比值升高;Gen显著上调RA患者BM-MSCs中OPG表达,对RANK、RANKL表达无明显影响,从而降低了RANKL/OPG比值,与E_2作用类似。免疫荧光结果显示:Gen能促进RA患者的BM-MSCs中ERα入核。结论Gen可能通过活化雌激素受体介导的相关信号通路,调控RA患者BM-MSCs中RANKL/OPG的表达,从而调节破骨细胞分化及成骨细胞分化,抑制RA关节破坏和促进受损关节的修复。展开更多
基金Supported by Shanghai Municipal Health Bureau Youth Grant, No. 2008Y032
文摘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
文摘目的研究金雀异黄素(Gen)对类风湿关节炎(RA)患者间充质干细胞(MSCs)中的核因子κB受体活化因子(RANK)、核因子κB受体活化因子配体(RANKL)和骨保护素(OPG)系统的影响及其机制。方法分离培养正常人与RA患者的骨髓MSCs(BM-MSCs),分为空白对照组、Gen处理组、雌二醇(E_2)处理组和Gen+雌激素受体拮抗剂(ICI182780)组,采用Western blot法检测BM-MSCs中RANK、RANKL、OPG的表达;采用免疫荧光法检测雌激素受体α(ERα)细胞内分布情况。结果 Western blot结果显示:与正常人BM-MSCs相比,RA患者BM-MSCs中的RANK的蛋白表达水平明显升高,OPG的蛋白表达水平明显降低,RANKL/OPG比值升高;Gen显著上调RA患者BM-MSCs中OPG表达,对RANK、RANKL表达无明显影响,从而降低了RANKL/OPG比值,与E_2作用类似。免疫荧光结果显示:Gen能促进RA患者的BM-MSCs中ERα入核。结论Gen可能通过活化雌激素受体介导的相关信号通路,调控RA患者BM-MSCs中RANKL/OPG的表达,从而调节破骨细胞分化及成骨细胞分化,抑制RA关节破坏和促进受损关节的修复。
