Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice
Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice
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DOI：
10.1038/aps.2009.77
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发表时间：
2009-07-01
影响因子：
8.2
通讯作者：
Hu, Jing
中科院分区：
文献类型：
--
作者：
Liu, Xiao-chang;Mei, Qiao;Hu, Jing
目的：研究巴柳氮对葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠肠粘膜通透性的影响，并探讨其作用机制。以42、141和423 mg/kg的剂量灌胃给予巴沙拉嗪。采用疾病活动指数（DAI）评分，并收集结肠组织进行组织学变化评估。测定结肠组织丙二醛（MDA）含量、髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性。收集小肠粘膜以测定肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ的水平。结果：Balsalazine可降低结肠炎小鼠的DAI评分和组织学指数（HI）评分，降低MDA含量和MPO活性，升高SOD和GSH-Px活性。同时，巴柳氮可改善结肠炎小鼠肠壁微绒毛和紧密连接结构，降低肠壁伊文思蓝渗透量，降低TNF-α和IFN-γ水平。结论：巴柳氮抗结肠炎小鼠结肠炎的作用是通过降低肠粘膜通透性实现的。其作用机制部分与巴柳秦的抗氧化和抗炎作用有关。
Aim: To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes.Methods: Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde (MDA) in the colon was determined, along with the activity of myeloperoxidase (MPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.Results: Balsalazine was found to reduce the DAI score and the histological index (HI) score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-alpha and IFN-gamma in colitis mice.Conclusion: In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects.