Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats
Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats
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3,4-氧代异丙叉莽草酸对大鼠实验性结肠炎的改善作用及其机制
DOI：
10.1016/j.intimp.2013.02.008
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发表时间：
2013-03-01
影响因子：
5.6
通讯作者：
Sun, Jianning
中科院分区：
文献类型：
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作者：
Xing, Jianfeng;You, Cuiyu;Sun, Jianning
本研究旨在探讨3,4-氧-异丙基莽草酸（ISA）对2,4,6-三硝基苯磺酸（TNBS）诱导大鼠结肠炎的治疗作用及其机制。在TNBS诱导结肠炎后第1天，分别给予50、100、200 mg/kg的剂量。通过宏观损伤评分和髓过氧化物酶（MPO）活性评估结肠损伤和炎症。采用生化法测定血浆丙二醛（MDA）、一氧化氮（NO）水平，以及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性。用放射免疫法测定结肠组织中前列腺素E-2 （PGE(2)）水平。免疫组织化学法检测诱导型一氧化氮合酶（iNOS）、环氧化酶-2 （COX-2）、抑制剂κ B- α (I κ B α)和核因子κ B (nf - κ B) p65蛋白在结肠组织中的表达。TNBS灌肠动物结肠黏膜损伤、炎症反应和氧化应激增强，表现为结肠黏膜损伤指数、MPO活性、MDA、NO和PGE水平显著升高(2)，结肠黏膜iNOS、COX-2和NF-kappa B p65蛋白表达显著升高，结肠黏膜I kappa B α蛋白表达显著降低。然而，在一定剂量的ISA处理下，这些参数被发现显著改善，特别是在100 mg/kg和200 mg/kg的剂量下。ISA对实验性结肠炎大鼠可能具有显著的治疗作用，可能与其抗氧化机制、抑制花生四烯酸代谢和调节I κ B α / nf - κ B p65表达有关。(C) 2013 Elsevier B.V.版权所有
The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. (50, 100, 200 mg/kg) was administered for 14 days, 1 day after the induction of colitis by TNBS. The colonic injury and inflammation were assessed by macroscopic damage scores and myeloperoxidase (MPO) activity. Malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma were measured with biochemical methods. Prostaglandin E-2 (PGE(2)) level in colon was determined by radioimmunoassay. Expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), inhibitor kappa B-alpha (I kappa B alpha) and nuclear factor kappa B (NF-kappa B) p65 proteins in the colonic tissue were detected with immunohistochemistry. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with TNBS, which was manifested as the significant increase in colon mucosal damage index, MPO activity, levels of MDA, NO and PGE(2), as well as the expressions of iNOS, COX-2 and NF-kappa B p65 proteins in the colonic mucosa, and the significant decrease in expressions of I kappa B alpha proteins in the colonic mucosa. However, these parameters were found to be significantly ameliorated in rats treated with ISA at given doses, especially at 100 mg/kg and 200 mg/kg. Administration of ISA may have significant therapeutic effects on experimental colitis in rats, probably due to its mechanism of antioxidation, its inhibition of arachidonic acid metabolism and its modulation of the I kappa B alpha/NF-kappa B p65 expression. (C) 2013 Elsevier B.V. All rights reserved.