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依那西普减轻三硝基苯磺酸诱导的实验性结肠炎:TNF-α 表达的作用。

Etanercept attenuates TNBS-induced experimental colitis: role of TNF-α expression.

机构信息

Department of Pathology, Universidade Federal de São Paulo-Escola Paulista de Medicina, UNIFESP, São Paulo, SP, Brazil.

出版信息

J Mol Histol. 2011 Oct;42(5):443-50. doi: 10.1007/s10735-011-9349-z. Epub 2011 Aug 24.

Abstract

Crohn's disease (CD) is associated with gut barrier dysfunction. Tumour necrosis factor-α (TNF-α) plays an important role into the pathogenesis of several inflammatory diseases because its expression is increased in inflamed mucosa of CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus, this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis factor alpha (TNF-α) antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non-treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats from group 4 presented significant improvement either of macroscopic or of histopathological damage in the distal colon. The gene expression of TNF-α mRNA, decreased significantly in this group compared to the TNBS non-treated group. The treatment with etanercept attenuated the colonic damages and reduced the inflammation caused by TNBS. Taken together, our results suggest that ETC attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-α downregulation.

摘要

克罗恩病(CD)与肠道屏障功能障碍有关。肿瘤坏死因子-α(TNF-α)在几种炎症性疾病的发病机制中起着重要作用,因为它在 CD 患者的炎症黏膜中表达增加。抗 TNF 治疗可显著改善黏膜炎症。因此,本研究旨在评估依那西普(ETC),一种肿瘤坏死因子-α(TNF-α)拮抗剂对 2,4,6-三硝基苯磺酸(TNBS)诱导的实验性结肠炎的影响。总共 18 只 Wistar 大鼠随机分为四组:(1)假手术:假手术诱导结肠炎;(2)TNBS:未治疗的诱导结肠炎;(3)ETC 对照组;(4)ETC 治疗诱导结肠炎。第 4 组大鼠在远端结肠的大体或组织病理学损伤方面均有明显改善。与未治疗的 TNBS 组相比,该组 TNF-α mRNA 的基因表达显著降低。ETC 的治疗减轻了结肠损伤并减轻了 TNBS 引起的炎症。综上所述,我们的结果表明,ETC 通过下调 TNF-α 来减轻 Wistar 大鼠 TNBS 诱导的肠道结肠炎。

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