炎性反应在慢性低灌注脑白质损伤中具有重要作用。如何调节炎性反应减轻损伤是探索低灌注脑白质损伤治疗措施的关注点。我们发现腺苷通过A2A受体抑制炎性反应，减轻慢性低灌注脑白质损伤，其机制主要是通过抑制巨噬细胞向脑浸润活化实现的。已证实巨噬细胞M1向M2极化，促进抗炎因子合成，减轻炎性反应。预实验发现低灌注脑白质损伤区存在明显的巨噬细胞M1向M2极化现象，与髓鞘损伤程度负相关。鉴于A2A受体是诱导巨噬细胞M2极化的主要调控因素。因此我们推测A2A受体诱导巨噬细胞M2极化，抑制炎性反应，减轻低灌注脑白质损伤，但其作用机制尚不明确。为此，本项目拟通过临床血和脑脊液标本结合动物实验，采用双光子功能显微成像技术、蛋白质谱分析术等技术，从整体及细胞水平探讨A2A受体诱导巨噬细胞M2极化在慢性低灌注脑白质损伤中的作用，明确A2A受体诱导巨噬细胞M2极化的信号通路。为慢性低灌注脑白质损伤机制及治疗提供新思路。

Inflammation play an important role in the white matter lesions induced by chronic cerebral hypoperfusion.It is focus on the modulation of inflammation to explore the treatment of ischemic white matter lesions.Our findings showed that activation of A2A receptor inhibited the inflammation, attenuated white matter lesions induced by chronic cerebral hypoperfusion.It is associated with the inhibition of macrophage activation in the white matter lesions induced by chronic cerebral hypoperfusion.Numerious studies have indicated that a switch of mcrophage from M1 to M2 phenotype promoted the synthesis of anti-inflammatory cytokines and inhibited the inflammation. We have found that there was a switch of mcrophage from M1 to M2 phenotype in white matter lesions induced by chronic cerebral hypoperfusion. Moreover, activation of A2A receptor promoted the macrophage M2 polarization. Therefore we believe that activation of A2A receptor promote macrophage M2 polarization and inhibit the inflammation in the white matter lesions induced by chronic cerebral hypoperfusion. However, the signal pathway remained uncleared. To investigate the signal pathway, time-lapse two-photon spectral confocal imaging and 2DLC-MS/MS was used to exam the role of macrophage M2 polarization in the anti-inflammatory effect of A2A receptor to the white matter lesions induced by chronic cerebral hypoperfusion. Furthermore, we also explore the signal pathway in the macrophage M2 polarization to supply the ideals to investigate the mechanism of white matter lesions induced by chronic cerebral hypoperfusion.