Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice
Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice
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DOI：
10.1016/j.intimp.2016.04.038
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发表时间：
2016-07-01
影响因子：
5.6
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
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作者：
Wu, Cong;Xu, Zheng;Huang, Kehe
白细胞介素-10（IL-10）缺陷型小鼠自发发生T细胞介导的结肠炎。以前的报道表明，苦参碱可以减轻三硝基苯磺酸（TNBS）引起的急性结肠炎的症状。然而，苦参碱是否影响慢性结肠炎仍然未知。在这项研究中，我们研究了苦参碱是否可以限制自发性结肠炎的症状及其潜在的分子机制。IL-10缺陷小鼠通过每天口服管饲法给予苦参碱或PBS对照，持续4周，并在第2周或第4周处以安乐死。我们测量了体重、结肠长度和重量以及组织学评分。我们还评估了结肠外植体培养物中IL-12/23 p40、IFN-γ和IL-17的自发分泌以及未分离的肠系膜淋巴结（MLN）细胞中IFN-γ和IL-17的分泌，并评估了结肠组织中IFN-γ、IL-17、IL-1 β和IL-6 mRNA的表达。此外，我们分析了未分离的MLN细胞中CD 4阳性和CD 8阳性细胞的比例。我们的研究结果表明，苦参碱治疗的小鼠表现出更好的体重恢复比对照组，结肠组织中的组织学评分和自发分泌的IL-12/23 p40，IFN-γ和IL-17在治疗的小鼠与对照组相比显着降低。在第4周，治疗组小鼠MLN中CD 4阳性细胞的比例显著小于对照组。与对照组相比，治疗组小鼠的细胞因子产生和IFN-γ和IL-17的mRNA表达均显著降低。两者合计，我们的研究结果表明，苦参碱可以改善自发发展的慢性结肠炎，可以被认为是慢性结肠炎的治疗选择。(C)2016爱思唯尔B. V.保留所有权利。
Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4 weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-gamma and IL-17 in colon explant cultures As well as IFN-gamma and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-gamma, IL-17, IL-1 beta and IL-6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-gamma and IL-17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-gamma and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis. (C) 2016 Elsevier B.V. All rights reserved.