生理情况下红细胞存在于血管内，在创伤、手术等情况下均能导致出血。我们发现在肿瘤微环境中，血管外红细胞及其释放的血红蛋白能促进肿瘤生长，主要与其诱导巨噬细胞募集、极化和血管生成相关，该发现申请人以第一作者已发表 (Yin, et al. J Immunol 2015)。在此基础上，我们假设血红蛋白参与了正常组织损伤中的修复过程。我们将通过皮肤伤口愈合模型、肢端缺血模型和心肌梗死模型，检测组织修复过程中血红蛋白对M2型巨噬细胞活化的影响及其相关信号通路，和对M2型巨噬细胞促血管生成能力的影响。此外，我们还将检测血红蛋白是否能促进干细胞增殖(我们已有初步证据)。本研究探索血红蛋白是否为机体组织修复的启动因素之一及其分子机制，并将为伤口愈合和心血管疾病的治疗提供新思路。

Red blood cells physiologically exist in the circulation. Several conditions such as trauma and surgery result in hemorrhage. Our previous work demonstrated that extravascular erythrocytes and hemoglobin promoted tumor growth and therapeutical resistance, which was associated with macrophage recruitment and polarization, as well as angiogenesis. This work was published in the Journal of Immunology, 2015. We hypothesize that hemoglobin participates in the process of normal tissue repairs. We will investigate the effect of hemoglobin on the macrophages activation and pro-angiogenesis capacity in the cutaneous wound model, hindlimb ischemia model and myocardial infarction model. Besides, we postulate that hemoglobin might stimulate stem cells proliferation in the normal tissues. We have primary data concerning stem cells. This work is to investigate the initiation effect of hemoglobin on tissue repair and will provide a novel therapeutical idea for the wound repair and cardiovascular diseases.