新型神经保护剂YC-6预防急性高原病的非人灵长类动物多组学研究

目前，临床药物不能满足预防急性高原病的巨大社会需求。大量报道表明，急性低压缺氧引起神经系统损伤，导致急性高原病首先表现出神经生理功能障碍的临床症状，因此我们首次提出神经保护预防急性高原病策略，并在前期神经保护剂孕酮的研究中得到初步证实（工作基础一）。在此基础上，项目拟进一步展开具有完全自主知识产权的新型神经保护剂YC-6（工作基础二）预防急性高原病研究。运用非人灵长类食蟹猴急性低压缺氧动物模型模拟急性高原病，通过经典的神经功能学评分、脑含水量测定、组织病理学以及生化指标评价YC-6的药效，同时，通过脑组织、白细胞的mRNA和蛋白质表达谱模式展示提供多组学证据。生物信息学分析结合验证实验进一步探讨急性高原病新的病理分子机制，阐明YC-6通过神经保护作用预防急性高原病的作用靶点。项目的完成将为急性高原病的研究提供新的动物模型和基础数据，为防治高原病药物研发提供新思路与靶点。

Currently, clinical drug to prevent acute high-altitude disease cannot meet the enormous needs of the community. A large number of reports indicated that nervous system injury caused by the acute hypobaric hypoxia firstly led to neurophysiological dysfunction symptoms in patients suffering from acute high-altitude disease. For the first time, we proposed the strategies of neuroprotection to prevent acute mountain sickness, which were supported by our previous research of neuroprotective agents progesterone in crab-eating macaque (Macaca fascicularis) model (working basis a ) . On this basis, the project plans to further study the prevention to acute high-altitude illness by YC-6 , a novel neuroprotectant with completely independent intellectual property rights ( working basis b). Using nonhuman primates crab-eating macaque animal models of acute hypobaric hypoxia to mimic acute high-altitude disease, pharmacodynamic efficacy of YC-6 will be evaluated not only by classical methods such as neurological function score , brain water content determination , histopathological and biochemical parameters ，but also by multi -omics evidence from mRNA and protein expression profiling mode in brain tissue and leukocytes. Bioinformatics analysis combined with validation experiments will be carried out to further explore the the new pathological molecular mechanism of acute mountain sickness , and illuminate the targets of YC-6 in the prevention of acute mountain sickness through neuroprotection . The project's accomplishment will provide new fundamental data and animal models for acute mountain sickness research , and supply new ideas and possible drug targets as well for prevention and treatment of high altitude disease.