Nrf2调控FUNDC1介导线粒体自噬在跨区穿支皮瓣choke血管重塑中的作用及机制研究

如何实现跨区穿支皮瓣高质量成活是目前临床未能解决的棘手难题。我们既往研究发现促进跨区穿支皮瓣choke血管重塑能扩大皮瓣存活面积；Nrf2的高表达可促进皮瓣的微血管新生。然而，Nrf2在choke血管重塑过程中的作用及机制仍不清楚。我们预实验发现Nrf2作为FUNDC1的上游转录因子，可促进其表达；有研究表明FUNDC1作为线粒体外膜蛋白在线粒体自噬过程中发挥重要作用；亦有研究显示自噬可上调VEGF、降低ROS促进皮瓣血管再生。故推测Nrf2调控FUNDC1介导choke血管内皮细胞线粒体自噬，继而上调VEGF、降低ROS促进跨区穿支皮瓣choke血管重塑。本研究拟采用基因沉默、蛋白信号干扰等手段，分别从细胞和动物实验层次分析Nrf2与FUNDC1、线粒体自噬相关特异性蛋白的相互关系，揭示Nrf2在choke血管重塑中的作用机制，旨在为临床预构血供可靠的跨区穿支皮瓣奠定理论基础。

Achieve high-quality survival of cross-regional perforator flaps has been a challenging problem in clinic. Our previous studies have shown that promoting the remodeling of choke vessels in cross-regional perforator flaps could expand the survival area of the flap, and increasing the expression of Nrf2 could promote the microangiogenesis of the flap. However, the mechanism of action of Nrf2 in choke vascular remodeling is still unclear. Studies have shown that autophagy could upregulate VEGF and downregulate ROS to promote flap vascular regeneration. Our preliminary experiments found that Nrf2, as an upstream transcription factor of FUNDC1, is able to enhance the expression of FUNDC1; some studies have shown that FUNDC1 plays an important role in mitochondrial autophagy as a mitochondrial outer membrane protein; therefore, we speculate that Nrf2 regulates FUNDC1-mediated choke vascular endothelial cell mitochondria Autophagy, which in turn upregulates VEGF and downregulates ROS, promotes choke vascular remodeling of transregional perforator flaps. Our study intends to use gene silencing and protein signal interference to analyze the relationship between Nrf2 and FUNDC1, mitochondrial autophagy-related specific proteins, and to reveal the mechanism of Nrf2 in the process of choke vascular remodeling. Reliable cross-regional perforator flaps lay the theoretical foundation.