期刊文献+

娃儿藤碱类化合物DCB-3503对TNBS诱导溃疡性结肠炎的治疗作用 被引量:2

Therapeutic effect of tylophorine analog DCB-3503 on TNBS-induced ulcerative colitis
原文传递
导出
摘要 目的探讨娃儿藤碱类化合物DCB-3503对三硝基苯磺酸(TNBS)诱导溃疡性结肠炎的治疗作用及可能的作用机制。方法选用C57BL/6野生型小鼠24只,分为对照(EtOH)组、实验(TNBS+DMSO)组、治疗(TNBS+DCB-3503)组。造模3 d后,观察各组间结肠长度、病理切片以及肠系膜淋巴结中IFN-γ+炎症性细胞和调节性T细胞(Treg)的差异。分离肠黏膜上皮细胞(IECs)总蛋白,Western blot检测Treg标志蛋白Foxp3的变化。结果治疗组损伤较实验组明显减轻,其肠系膜淋巴结中IFN-γ+细胞显著减少,Treg细胞显著增多,且IECs中Foxp3表达明显上调。结论在溃疡性结肠炎中,DCB-3503通过诱导T细胞分化为Foxp3+Treg细胞,从而抑制IFN-γ+炎症性细胞发挥作用,最终缓解肠道的炎症反应。 Objective To evaluate the protective effect of tylophorine DCB-3503 on trinitrobenzene sulfonic acid ( TNBS) induced ulcerative colitis and the possible molecular mechanism. Methods 24 C57BL/6 wild-type mice were di- vided into three groups : EtOH group, TNBS + DMSO group and TNBS + DCB-3503 group. Three days after the model was set up, the mice were killed and colon length, histological section, patterns of IFN-γ inflammatory cells and Treg cells were examined. Besides, the expression of Foxp3 in IECs was detected using Western blot. Results Compared with TNBS + DMSO group, DCB-3503 treatment group displayed remarkably improved clinical symptoms. Percentage of IFN-,,/~ inflammatory cells in mesenteric lymph node was significantly decreased in TNBS + DCB-3503 group. Meanwhile the percentage of Treg cells in mesenteric lymph node and the expression of Foxp3 in intestinal epithelial cells (IECs) were significantly increased after DCB-3503 treatment. Conclusion The increase of Treg cells and de- crease of IFN-γ inflammatory cells in DCB-3503 treatment group suggest that DCB-3503 can ameliorate the ulcerative colitis induced by TNBS via the growing number of Foxp3 Treg cells and their suppression on IFN-γ, inflammatory cells.
出处 《山东大学学报(医学版)》 CAS 北大核心 2012年第10期81-85,共5页 Journal of Shandong University:Health Sciences
关键词 溃疡性结肠炎 三硝基苯磺酸 IFN-γ TREG FOXP3 Ulcerative colitis Trinitrobenzene sulfonic acid IFN-γ Treg Foxp3
  • 相关文献

参考文献21

  • 1Wirtz S, Neufert C, Weigmann B, et al. Chemically in- duced mouse models of intestinal inflammation [ J ] Nat Protocol, 2007, 2:541-546.
  • 2Kaser A, Zeissig S, Blumberg R S. Inflammatory bowel disease[J]. Annu Rev Immunol, 2010, 28:573-621.
  • 3Gao W, Lam W, Zhong S, et al. Novel mode of action of tylophorine analogs as antitumor compounds [ J ]. Canc- er Res, 2004, 64(2) :678-688.
  • 4You X, Pan M, Gao W, et al. Effects of a novel tylo- phorine analog on collagen-induced arthritis through inhi- bition of the innate immune response [J]. Arthritis Rheum, 2006, 54(3):877-886.
  • 5Choi J Y, Gao W, Odegard J, et al. Abrogation of skin disease in LUPUS-prone MRL/FASlpr mice by means of a novel tylophorine analog [ J ]. Arthritis Rheum, 2006, 54(10) :3277-3283.
  • 6Ito R, Shin-Ya M, Kishida T, et al. Interferon-gamma is causatively involved in experimental inflammatory bowel dis- ease in mice[J]. Clin Exp Immunol, 2006, 146:330-338.
  • 7Sakaguchi S, Sakaguchi N. Regulatory T cells in immu- nologic self-tolerance and autoimmune disease [ J ]. Int Rev Immunol, 2005, 24:211-226.
  • 8Jonuleit H, Schmitt E, Stassen M, et al. Identification and functional characterization of human CD4 ( + ) CD25 ( + ) T cells with regulatory properties isolated from pe- ripheral blood[J]. J Exp Med, 2001, 193:1285-1294.
  • 9Sakaguchi S, Wing K, Yamaguchi T. Dynamics of pe- ripheral tolerance and immune regulation mediated by Treg [J].Eur J Immunol, 2009, 39:2331-2336.
  • 10Liston A, Rudensky A Y. Thymic development and pe- ripheral homeostasis of regulatory T cells[J]. Curr Opin Immunol, 2007, 19 : 176-185.

二级参考文献13

  • 1Lakatos L,Lakatos P L.Etiopathogenesis of inflammatory bowel diseases[J].OrvHetil,2003,144 (38):1853-1860.
  • 2Jonaleit H,Adema G,Schmitt E.Immune regulation by regulatory T cells:implications for transplantataion[J].Transpl Immunol,2003,11 (3-4):267-276.
  • 3Yokoyama Y,Fukunagu K,Fukuda Y,et al.Demonstration of Low-Regulatory CD25High +CD4 + and High-Pro-inflammatory CD28-CD4+T-Cell Subsets in Patients with Ulcerative Colitis:Modified by Selective Granulocyte and Monocyte Adsorption Apheresis[J].Dig Dis Sci,2007,52 (10):2725-2731.
  • 4Jonuleit H,Adema G,Schmitt E.Immune regulation by regulatory T cells:implications for transplantataion[J].Transpl Immunol,2003,11 (3-4):267-276.
  • 5Asano M,Toda M,Sakaguchi N et al.Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation[J].J ExpMed,1996,184(2):387-396.
  • 6Hori S,Nomura T,Sakaguchi S.Control of regulatory T cell development by the transcription factor Foxp3[J].Science,2003,299(5609):1057-1061.
  • 7Fontenot J D,Rudensky A Y.A well adapted regulatory contrivance:regulatory T cell development and the forkhead family transcription factor Foxp3[J].Nat Immunol,2005,6(4):331-337.
  • 8Fontenor Z,Gavinm A,Rudensky A Y.Foxp3 programs the development and function of CD4+CD25+T regulatory cells[J].Nat Immunol,2003,4(4):330-336.
  • 9Walker M R,Kasprowicz D J,Gersuk V H,et al.Induction of Foxp3 and acquisition of T regulatory activity by stimulated human CD4+CD25-T cells[J].J Clin Invest,2003,112 (9):1437-1443.
  • 10Wan Y Y,Flavell R A.Regulatory T-cell functions are subverted andconverted owing to attenuated Foxp3 expression[J].Nature,2007,445 (7129):766-770.

共引文献4

同被引文献10

引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部