通过Bim/Beclin1调控Treg自噬/凋亡平衡对动脉粥样硬化进程影响的研究

Atherosclerosis (AS) is an inflammatory disease, in which T cells play key roles. Regulatory T cell (Treg) reduces AS by decreasing the level of activation, proliferation and cytokine production of effector T cells. In AS, the quantity and function of Treg decreased. Treg homeostasis is related to its differentiation, proliferation and susceptibility to death. The autophagy/apoptosis banlace contribute to Treg's susceptibility to death., and there is few study about the autophagy/apoptosis banlace of Treg in AS. Bim preferentially control the apoptosis of Treg; Beclin1 is the key molecule for autophagy; and Bim inhibits autophagy by interacting with Beclin 1. The present study will observe the Bim/Beclin1 ratio and the autophagy/apoptosis banlace of Treg in AS; and investigate the effect of Bim or Beclin1-Depleted and -Overexpressing Tregs on autophagy/apoptosis banlace in vitro and AS prosgress in vivo, which will contribute to protecting against AS.

炎症/免疫活化是动脉粥样硬化（AS）的重要发病机制，T细胞在其中发挥关键作用。调节性T细胞（Treg）通过抑制效应性T细胞的促炎症活动而减缓AS进程。在AS进程中Treg数量和功能下降。Treg的自身稳态与其分化增殖和存活能力均相关。自噬/凋亡平衡对Treg的存活能力有着关键影响。目前关于Treg在AS进程中的自噬/凋亡平衡鲜有研究。Bim蛋白对Treg凋亡发挥特异性控制作用；Beclin1是自噬必需蛋白；Bim可直接抑制Beclin1作用。本研究拟在已有工作基础上，探明Bim/Beclin1比例及Treg 自噬/凋亡平衡在AS发展不同阶段的水平；通过构建Bim或Beclin1过度表达(转基因)/表达抑制（RNAi）的Treg，观察Bim/Beclin1比例改变对Treg 自噬/凋亡平衡及AS斑块发生发展和稳定性的影响，为探讨AS防治新战略提供依据。