间充质干细胞通过TGF-β调控调节性T细胞治疗肠道缺血再灌注损伤的机制研究

项目名称： 间充质干细胞通过TGF-β调控调节性T细胞治疗肠道缺血再灌注损伤的机制研究

项目编号： No.81201463

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 杨薛康

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 我们前期实验发现，移植间充质干细胞（MSCs）能减轻大鼠缺血再灌注损伤（IRI）诱导的肠道炎症反应，保护受损肠道，但机制仍不明确。既往研究表明，负向调控炎症反应的调节性T细胞（Treg）在脏器IRI过程中发挥了中心性的保护作用。我们进一步研究发现，炎症刺激可促进MSCs分泌TGF-β，而TGF-β是诱导Treg生成的主要因子，提示MSCs可能通过分泌TGF-β上调Treg水平，抑制炎症反应，进而保护IRI的脏器。本课题拟在大鼠肠道缺血再灌注（GIR）损伤模型中，通过移植对照和抑制Treg水平后，在体实验检测Treg变化，促炎/抗炎因子、肠道粘膜通透性变化，明确Treg在MSCs治疗GIR损伤中的作用；进一步体内外实验，通过干涉或过表达TGF-β的MSCs，探讨MSCs与Treg相互作用在调控炎症反应过程中的机制，为临床应用MSCs治疗GIR损伤提供理论基础。

中文关键词： 肠道；缺血再灌注损伤；间充质干细胞；炎症；调节性T细胞

英文摘要： Our earlier study demonstrated that the transplantation of mesenchymal stem cells (MSCs) can reduce ischemia reperfusion injury (IRI)-induced intestinal inflammation and protect the damaged intestinal tract, but the mechanism remains unclear. Previous studies have shown that the regulatory T cells (Treg), which negatively regulate inflammation, play a central protective effect in the process of organ IRI. We further found that inflammatory stimuli can promote MSCs secret TGF-β, the main factor that induced Treg generation. The results suggested that MSCs may upregulate Treg levels by secreting TGF-β to inhibit inflammatory response, thereby protect the organs of IRI. After transplanting MSCs control and suppressing Treg level in a rat model of intestinal ischemia reperfusion injury (GIR), we intend to clarify the role of Treg in the MSCs treatment of GIR injury by detecting in vivo the changes of Treg, pro-inflammatory/anti-inflammatory factors, and intestinal mucosal permeability. Further experiments in vitro and in vivo, with interference or overexpression of TGF-β in MSCs, we try to explore the interaction mechanisms of MSCs and Treg in regulating inflammatory response, therefore to provide a theoretical basis for the clinical application of the MSCs treatment of GIR injury.

英文关键词： Intestine； ischemia-reperfusion injury ；mesenchymal stem cells ；inflammation； regulatory T cells