MG Pharma Inc., 7-7-25, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Life Sci. 2012 Jan 30;90(5-6):190-9. doi: 10.1016/j.lfs.2011.11.013. Epub 2011 Dec 1.
We investigated the effects of globin digest (GD) and its active ingredient Trp-Thr-Gln-Arg (WTQR) on galactosamine/lipopolysaccharide (GalN/LPS)-induced liver injury in imprinting control region (ICR) mice.
The effects of WTQR and GD on the liver injury were examined by measuring the survival rate, serum aminotransferase activities, hepatic components, antioxidant enzyme activities, histopathological analysis, serum levels and hepatic gene expression of tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2), and nitric oxide (NO) or inducible nitric oxide synthase (iNOS), and nuclear factor-kappa B (NF-κB) p65 content in GalN/LPS-treated ICR mice. RAW264 mouse macrophages were used to confirm the anti-inflammatory effects of WTQR and GD on the macrophages.
WTQR and GD increased the survival rate, suppressed the serum aminotransferase activities, serum levels and hepatic gene expression of TNF-α, MIP-2, and NO or iNOS, and nuclear NF-κB p65 content in GalN/LPS-treated mice; decreased the oxidized glutathione content, increased the superoxide dismutase activity, and decreased the histopathological grade values of the hepatocyte necrosis and lobular inflammation in GalN/LPS-injured liver; and suppressed the release levels and gene expression of TNF-α, MIP-2, and NO or iNOS, and nuclear NF-κB p65 content in LPS-stimulated RAW264 macrophages. WTQR and GD may improve the antioxidant defense system and inflammatory status in GalN/LPS-injured liver.
These findings indicate that WTQR and GD have hepatoprotective effects on GalN/LPS-induced liver injury in ICR mice.
我们研究了球蛋白消化产物(GD)及其活性成分色氨酰-苏氨酰-谷氨酰-精氨酰(WTQR)对半乳糖胺/脂多糖(GalN/LPS)诱导的 ICR 小鼠肝损伤的影响。
通过测量存活率、血清转氨酶活性、肝组织成分、抗氧化酶活性、组织病理学分析、血清水平和肝组织肿瘤坏死因子-α(TNF-α)、巨噬细胞炎症蛋白-2(MIP-2)和一氧化氮(NO)或诱导型一氧化氮合酶(iNOS)的基因表达,以及 GalN/LPS 处理的 ICR 小鼠核因子-κB(NF-κB)p65 含量,研究 WTQR 和 GD 对肝损伤的影响。使用 RAW264 小鼠巨噬细胞来确认 WTQR 和 GD 对巨噬细胞的抗炎作用。
WTQR 和 GD 提高了 GalN/LPS 处理小鼠的存活率,抑制了血清转氨酶活性、血清 TNF-α、MIP-2、NO 或 iNOS 水平和肝组织基因表达,以及核 NF-κB p65 含量;降低了氧化型谷胱甘肽含量,增加了超氧化物歧化酶活性,降低了 GalN/LPS 损伤肝的肝细胞坏死和小叶炎症的组织病理学分级值;抑制了 LPS 刺激的 RAW264 巨噬细胞中 TNF-α、MIP-2、NO 或 iNOS 的释放水平和基因表达,以及核 NF-κB p65 含量。WTQR 和 GD 可能改善了 GalN/LPS 损伤肝的抗氧化防御系统和炎症状态。
这些发现表明,WTQR 和 GD 对 ICR 小鼠 GalN/LPS 诱导的肝损伤具有保护作用。