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葡萄籽原花青素通过调节核因子-κB 信号转导通路治疗三硝基苯磺酸诱导的大鼠复发性溃疡性结肠炎

Proanthocyanidins from grape seeds modulates the nuclear factor-kappa B signal transduction pathways in rats with TNBS-induced recurrent ulcerative colitis.

机构信息

Department of Pharmacy, People's Hospital of Gansu Province, Lanzhou 730000, Gansu, China.

出版信息

Int Immunopharmacol. 2011 Oct;11(10):1620-7. doi: 10.1016/j.intimp.2011.05.024. Epub 2011 Jun 12.

DOI:10.1016/j.intimp.2011.05.024
PMID:21642017
Abstract

The aim of this study was to elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE) on recurrent ulcerative colitis (UC) in rats. GSPE in doses of 100, 200, and 400mg/kg were intragastrically administered per day for 7 days after recurrent colitis was twice-induced by TNBS. The levels of GSH, as well as the activity of GSH-Px and SOD in colon tissues were measured by biochemical methods. The expression levels of tumor necrosis factor-α (TNF-α) and the nuclear translocation levels of nuclear factor-kappa B (NF-κB) in the colon tissues were measured by enzyme-linked immunosorbent assay methods. Western blotting analysis was used to determine the protein expression levels of inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), phosphorylated IκBα and phosphorylated IKKα/β. GSPE treatment was associated with a remarkable increased the activity of GSH-Px and SOD with GSH levels in TNBS-induced recurrent colitis rats as compared to the model group. GSPE also significantly reduced the expression levels of TNF-α, p-IKKα/β, p-IκBα and the translocation of NF-κB in the colon mucosa. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response and promoting damaged tissue repair to improve colonic oxidative stress. Moreover, GSPE inhibited the TNBS-induced inflammatory of recurrent colitis though blocking NF-κB signaling pathways.

摘要

本研究旨在阐明葡萄籽原花青素(GSPE)治疗大鼠复发性溃疡性结肠炎(UC)的作用机制。采用 TNBS 两次诱导复发性结肠炎后,每天通过胃内给予 GSPE 100、200 和 400mg/kg,连续 7 天。采用生化方法测定结肠组织中 GSH 的水平以及 GSH-Px 和 SOD 的活性。采用酶联免疫吸附试验方法测定结肠组织中肿瘤坏死因子-α(TNF-α)的表达水平和核因子-κB(NF-κB)的核转位水平。采用 Western blotting 分析测定抑制性κB-α(IκBα)、抑制性κB 激酶(IKKα/β)、磷酸化 IκBα 和磷酸化 IKKα/β的蛋白表达水平。与模型组相比,GSPE 治疗可显著提高 TNBS 诱导的复发性结肠炎大鼠 GSH-Px 和 SOD 的活性和 GSH 水平。GSPE 还可显著降低结肠黏膜中 TNF-α、p-IKKα/β、p-IκBα和 NF-κB 的转位表达。GSPE 通过调节炎症反应和促进受损组织修复来改善结肠氧化应激,从而对大鼠复发性结肠炎发挥保护作用。此外,GSPE 通过阻断 NF-κB 信号通路抑制 TNBS 诱导的复发性结肠炎的炎症反应。

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