跨区穿支皮瓣是皮肤缺损修复的常用术式，缺血缺氧导致皮瓣坏死仍是临床难题。我们前期研究发现：(1)中央型穿支能促使皮瓣成活范围最大化，坏死仅发生于潜在区。(2)与氧化应激损伤相比，促进血管化对提高皮瓣成活更为重要。(3)炎症参与的动脉生成与动力区成活有关。动脉生成不足在潜在区坏死中起重要作用，而血管内皮细胞的Trpv4是激活动脉生成的起始靶点，随后由单核细胞参与动脉生成。因此我们提出内皮细胞Trpv4/ERK通路诱导的单核细胞激活对跨区穿支皮瓣动脉生成起到关键性调节作用的假说，本项目拟通过药物和基因手段调控脐静脉内皮细胞Trpv4/ERK通路，观察其对单核细胞的作用及通路相关信号分子表达，同时建立SD大鼠跨区穿支皮瓣动物模型，通过药物调控研究Trpv4/ERK通路激活单核细胞对皮瓣动脉生成的影响，本研究将深入揭示Trpv4/ERK诱导的单核细胞激活对跨区穿支皮瓣动脉生成的意义及其机制。

Multiterritory perforator flap is a common procedure for skin defect, flap necrosis caused by ischemia is still a clinical problem. Our previous studies found that: (1) A central perforator could support a larger flap and necrosis only occurred in the potential perforasome. (2) Promoting flap vascularization was more important for improving flap survival when compared with oxidative stress injury. (3) The arteriogenesis was responsible for dynamic perforasome survival, and inflammation was involved in the process of arteriogenesis. Insufficient arteriogenesis plays an important role in the potential perforasome necrosis. Trpv4 is the initial target for the activation of arteriogenesis in the endothelial cells, and then monocytes are involved in the process of arteriogengsis. Therefore, we hypothesize that the activation of monocytes induced by the Trpv4/ERK pathway of endothelial cells plays a key role in the regulation of arteriogenesis. In this project, we use drugs and gene methods to regulate Trpv4/ERK pathway in the umbilical vein endothelial cells. We will investigate its effects on monocyte and the expression of signal molecules. Then, we use drugs regulation to elucidate the effect of Trpv4/ERK-induced-monocyte activation on the arteriogenesis in a SD rat perforator flap model. This study will further reveal the significance of Trpv4/ERK-induced-monocyte activation on the arteriogenesis and its mechanism.