高原低氧损伤可导致机体记忆能力下降，该过程同大脑神经元线粒体损伤有关，目前尚无理想防治药物。我们前期研究发现HPN对高原缺氧具有保护作用，以此为线索，提出假设：将HPN同线粒体靶向基团结合而合成的Mito-HPN可能具有更好的抗高原缺氧作用。行为学预实验结果提示Mito-HPN具有较好的缺氧记忆保护效果，但其机制不明。为验证假设，拟建立小鼠和PC12细胞缺氧模型，应用RNA干扰技术调控Nrf2的表达，并应用工具试剂干预缺氧状态下PGC-1α/Nrf2/TFAM信号通路，采用透射电镜、Western blot等技术，观察Mito-HPN对缺氧小鼠大脑神经元和PC12细胞坏死、凋亡、线粒体形态的保护作用。旨在认识Mito-HPN调控线粒体生物合成的作用，并揭示其细胞内信号通路机制，以阐明高原低氧造成记忆损伤的发病机制。本研究将从线粒体靶向这个新视点为研发高原缺氧损伤防治药物提供新的思路。

High altitude hypoxia could lead to memory impairment, which was related to the damage of mitochondrial in brain neurons. There was no ideal control medicines. Our previous study found that HPN has protective effects on the high altitude hypoxia. According to which, we hypothesized: Mito-HPN synthesized by combining HPN with mitochondrial targeting group might have better protective effects against high altitude hypoxia. The behavior experimental results showed that Mito-HPN had better memory protective effect against hypoxia, but the mechanism was still unknown. To test the hypothesis, we intended to establish mouse and PC12 cells hypoxia model, using RNA interference technology to regulate Nrf2 gene expression, applicating tools reagents to intervent PGC-1α/Nrf2/TFAM signaling pathway under hypoxia conditions, using transmission electron microscopy and western blot techniques, to observe the protective effect of Mito-HPN on mouse brain neurons and PC12 cell to hypoxia necrosis, apoptosis, and mitochondrial morphology. The purpose of the regulation was to recognize role of Mito-HPN in mitochondrial biogenesis and reveal its cell signaling pathway mechanisms, in order to clarify the pathogenesis of memory impairment during high altitude hypoxia. This study could provide new ideas for the research development of high altitude hypoxia injuries prevention drugs from mitochondrial targeted radical scavengers perspectives.