深入揭示缺血缺氧性脑损伤的病理生理机制、提高其干预治疗效果一直是神经科学领域的研究重点和难点。申请者在前期国家自然科学基金的研究发现并证实了Id2(inhibitor of DNA binding 2)蛋白在缺血缺氧性神经元中表达显著上升，促使了神经元的凋亡；生化实验更揭示Id2对神经元中Rb/E2F1通路的枢纽调控作用。进一步的预初实验研究发现c-Myc能够结合到Id2的启动子区域，调控Id2的转录；且在脑缺血缺氧损伤中，c-Myc核定位亦呈现异常升高；而c-Myc特异的小分子抑制剂（10058-F4）减小了缺血缺氧后脑梗塞面积，提示Id2在缺血缺氧性脑损伤中极有可能受到c-Myc的上游调控作用。拟进一步通过分子、细胞及动物的研究，深入探讨c-Myc在缺血缺氧性脑损伤中对Id2的作用机制及其干预研究，克服了Id2靶向抑制剂缺乏的困难，还为缺血缺氧性脑损伤提供新的科学理论和新的干预手段。

Further reveal the pathophysiological mechanism of ischemia/hypoxic-induced brain injury and improve the effect of its intervention therapy are important and difficult to neuroscience researchers. Through the researches granted by National Science Foundation, applicant previously discovered and confirmed that the expression of Id2 (inhibitor of DNA binding 2) was up-regulated significantly in neuronal cells after the exposure of hypoxic/ischemia, ptomoted the neuronal apoptosis; Biochemical experiments reveal more Id2 plays pivotal control of neurons in the Rb/E2F1 pathways. Further preliminary experiments found that c-Myc can combine with Id2 promoter regions, regulate the transcription of Id2; c-Myc’s nuclear localization also unusually increased in ischemia/hypoxic-induced brain injury; Application of c-Myc specific small molecule inhibitors (10058-F4) could reduce ischemia/hypoxia after brain infarct size, implicate Id2 is likely to be regulated by c-Myc in the ischemia/hypoxic-induced brain injury. Based on these research results above, the applicant intends to further research a new mechanism that c-Myc regulates Id2 in hypoxic/ischemia-induced brain injury and its intervention study the through the molecules, cells and animal research. Provides new scientific theory for ischemia/hypoxic-induced brain injury; Not only overcome the difficulty of Id2 small molecular inhibitors’ absence, c - Myc specific small molecule inhibitors also provides a new feasible method for clinical intervention treatment.