现代社会发展节奏加快，疲劳已成为一个日益突出的社会问题，深入研究疲劳发生的机制意义重大。本项目从蛋白质组学入手，发现了一个全新的内源性抗疲劳蛋白ORM1，在骨骼肌细胞上有其结合位点，我们拟在此基础上，深入探讨ORM1抗疲劳作用的受体机制。首先继续检测各种疲劳模型后ORM1的组织表达谱，以及ORM1的靶器官和组织细胞定位；其次通过ORM1过表达和敲除动物，明确ORM1在抗疲劳中的关键地位；然后，进一步明确ORM1受体存在，鉴定该受体并阐明其作用机制（以骨骼肌为主）；最后在整体动物水平，利用靶受体敲除动物，验证ORM1抗疲劳作用的受体机制。本项目的完成，将阐明一个全新的内源性抗疲劳蛋白ORM1及其受体作用机制，同时也为新的抗疲劳药物的开发提供新思路。

Fatigue has been become a prominent social problem with the development of moderlizatioin, and deep mechanism studies about how fatigue happen and develep remains urgency.Our previous studies found a new endougenous anti-fatigue protein, ORM1, which has a binding site in C2C12 skeletal muscle cells. In present study, we plan to further clarify the receptor-mechanism of ORM1. First, ORM1 tissue expression profile should be decteced in various fatigue model, and its target organs and cell localization should also be clarifeid. Second, clarifying the key status of ORM1 in anti-fatigue role by using the ORM1 overexpression or knockdown mice.Third, based on the definite existence of receptor in skeletal muscle cell or other cells, we further identified this receptor and elucidate is signal transduction pathway.Last, we will observe the influence of target receptor knockdown on the anti-fatigue role of ORM1 in mice, and further ascertain the receptor mechanism of ORM1. The completion of this project will provide new sight in the field of exploring new anti-fatigue drugs.