调节性T细胞在心肌缺血再灌注损伤中的作用和机制研究

近年来研究显示心肌缺血再灌注损伤（MIRI）与T细胞介导的免疫炎症关系密切。调节性T细胞（CD4+CD25+FOXP3+Treg）是具有免疫调节作用的细胞群，可以分为天然性（nTreg）和诱导性（iTreg）两种，其生物学功能及在疾病中的作用不尽相同。我们前期的研究证实，MIRI后5分钟即有调节性T细胞（CD4+CD25+FOXP3+Treg）浸润心肌组织，过继转输体外激活的nTreg明显减轻MIRI。因此，我们认为Treg在MIRI中具有保护作用，其具体效应机制有待进一步阐明。本研究试图探讨：去除或增加Treg对MIRI的影响；MIRI中Treg通过何种调节性分子发挥保护作用；Treg对MIRI相关细胞生物学功能的影响；不同Treg亚群在该过程中作用是否相同。最终全面深入地阐明Treg在MIRI炎症调控中的保护作用和机制，为MIRI炎症的靶向治疗提供新的理论基础和实验依据。

Recent studies show that T cell-mediated inflammation is closely related to myocardial ischemia/reperfusion injury (MIRI). Regulatory T cells (Tregs) (CD4+CD25+FOXP3+Treg) is a subset of T cells with immunomodulatory function. There are both natural (nTregs) and inducible (iTregs) populations of Tregs, which may have complementary and overlapping functions in the effect of biological properties and control of immune responses. We found that regulatory T cells (Treg) infiltrated the myocardium as early as 5 minutes after MIRI and adoptive transfer of in-vitro activated nTreg markedly attenuated mouse MIRI. Therefore, we believe that Treg is protective in MIRI and the detailed mechanism of its regulation needs to be elucidated. The present research aims to explore the effects of Treg depletion or replenishment on MIRI, the functional mediators (IL-10/TGF-β1/adenosine) of Treg activity, the effects of Treg on endothelial activation, neutrophil infiltration, activation and reactive oxygen outbreak, cardiomyocyte apoptosis and chemokine secretion, and finally to elucidate the specific roles of Treg subsets (nTreg and iTreg). These exploratory studies will lead to a comprehensive understanding of the role of Treg in MIRI, and provide the theoretical and experimental basis for the development of targeted therapy in MIRI.