学习与记忆减退是高原病可出现的神经系统症状。作为NMDA受体的亚单位，NR3A的持续表达会引起小鼠学习与记忆减退。我们前期研究发现，大鼠脑缺血再灌注损伤时NR3A表达减少，辛伐他汀预处理起到保护作用时，其表达增加。在成年大鼠海马组织中还观察到NR3A与NR1具有蛋白交联关系。这些研究结果提示，NR3A参与了一些神经系统疾病或病理生理机制，同时可能存在含有NR3A的NMDA受体。由此，本课题提出，NR3A的功能性表达变化参与了高原低氧引起的学习与记忆减退。课题拟通过构建成年大鼠高原低氧学习记忆减退模型，分析NR3A的功能性表达变化及含有NR3A的NMDA受体构成，以期阐明NR3A在高原低氧引起学习记忆减退中的作用，为高原病中学习与记忆减退的预防和治疗寻找分子靶标，也为保护学习记忆的藏药开发提供参考依据。

The decline of learning and memory is neurological symptom that appears in high altitude disease. As a subunit of NMDA receptor, the persistent expression of NR3A can render the decline in learning and memory of mice. In previous study, we found that the expression of NR3A decreased during brain ischemia and reperfusion occurring in rats, however, increased as pretreatment of simvastatin making protective effects. In hippocampus of adult rats, we also observed that NR3A could interact with NR1. These findings suggested that NR3A participated in some neurological diseases or pathophysiological mechanisms, and meanwhile, NMDA receptor containing NR3A may exist. Thus this study proposed that the functional expression of NR3A may take part in the decline of learning and memory which caused by hypoxia at high altitude. In this application, we will first make an adult rat model with learning and memory decline in hypoxia at high altitude, and then analyze the functional expression of NR3A, and the institute of NMDA receptor that containing NR3A. The aim of this study is to clarify the effects of NR3A in learning and memory decline that rendered by hypoxia at high altitude, and to find the target for prevention and treatment of learning and memory decline in high altitude disease. Our study will also provide reference for the development of Tibetan drugs in protecting learning and memory.

脑是对缺氧极为敏感的器官，高原低氧可引起学习记忆减退。NMDA受体已被公认是学习记忆形成的重要参与者，其受体亚单位的表达变化与受体激活状态及参与的功能活动有关。本课题先通过低压氧舱模拟5000米、7000米海拔，缺氧2天、4天或6天，再用Morris水迷宫分析高原低氧对大鼠空间学习记忆的影响，继而又从基因、蛋白水平分析NMDA受体亚单位的参与作用。研究结果表明，与平原常氧组比，仅5000米6天组大鼠第4天逃避潜伏期延长，其它各组大鼠第4天、第5天逃避潜伏期与跨越平台次数均无显著变化。随海拔升高、缺氧时间延长，大鼠血清SOD/MDA比值增大，海马神经元损伤加重，海马CA1区NR1表达增加，NR2A、NR2B和NR3A表达减少。此外，高原低氧还引起大鼠出现一过性体重减轻及高原红细胞增多症。成年SD大鼠对高原低氧有一定抵抗性，尽管大鼠空间学习记忆能力未出现明显减退，但海马CA1区NMDA受体亚单位表达变化与海拔高度、缺氧时间相关，该受体激活状态如何还有待进一步研究。