骨骼肌挫伤是人体常见的软组织损伤类型之一。我们前期研究表明，2型大麻素受体（CB2R）在骨骼肌挫伤修复过程中通过调节炎症及纤维化相关因子对炎症反应及纤维化修复起到重要的作用，激动CB2R有益于骨骼肌再生。Nrf2是抗氧化反应的中枢调节因子，调控氧化应激反应、内质网应激和自噬相关的信号通路，在炎症反应、细胞凋亡、坏死、器官损伤修复与再生中发挥重要的作用。研究表明，CB2R可通过PI3K/Akt/Nrf2信号通路促进心肌细胞再生，提示在骨骼肌挫伤中CB2R可能通过Nrf2调控炎症反应、纤维化修复及骨骼肌再生过程。本项目应用Nrf2基因敲除鼠及基因沉默细胞，通过CB2R激动剂干预,采用分子生物学技术研究Nrf2对骨骼肌挫伤后氧化反应、纤维化修复、卫星细胞增殖、分化与骨骼肌再生的调节作用，探讨CB2R通过Nrf2调控骨骼肌挫伤修复的分子机制，为骨骼肌损伤、疾病的治疗及相关药物研发提供基础依据。

Skeletal muscle contusion is one of the common types of soft tissue injuries in human. Our previous studies indicate that cannabinoid receptor type 2 (CB2R) plays important roles in modulation of inflammatory reaction and fibrogenesis by regulating inflammation- and fibrogenesis-related cytokines during repair of skeletal muscle contusion, and we also found that CB2R agonism reveals beneficial effect on skeletal muscle regeneration after contusion. Much evidence has demonstrated that Nrf2 (nuclear factor-erythroid derived 2-related factor 2) is a pivotal factor in modulation against oxidative stress, which plays important parts in inflammatory reaction, apoptosis, necrosis, repair and cell regeneration in organs through pathways modulating anti-oxidative stress, endoplasmic reticulum stress and autophagy. A recent study shows that CB2R agonism may induce myocardial regeneration by PI3K/Akt/Nrf2 signaling pathway activation. It is suggested that CB2R may regulate inflammatory reaction, fibrogenesis, and muscle regeneration by Nrf2. The present project is attempted to study the roles of Nrf2 in modulating oxidative reaction, fibrogenesis, satellite proliferation and differentiation, and muscle regeneration with CB2R agonist intervention in Nrf2-knockout mice and Nrf2-knockdown cells by molecular biological techniques, and investigate the molecular mechanisms by which CB2R regulates repair of contused skeletal muscles through Nrf2 modulation. The study may also provide fundamental data for clinical treatment of traumatic muscle lesions and muscular diseases, and even for research and development for related drugs.