Zhang Zhijia, Hou Yuxing, Li Jiantao, Tang Chao, Que Linli, Tan Qian, Li Yuehua
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Department of Plasticsurgery, Drum Tower Hospital, Nanjing, Jiangsu 211100, China.
J Biomed Res. 2019 Jul 31;34(5):343-350. doi: 10.7555/JBR.33.20190030.
Morphological and functional abnormalities of vascular endothelial cells (VECs) are risk factors of ischemia-reperfusion in skin flaps. Signaling pathway mediated by interleukin-1 receptor (IL-1R) is essential to hypoxia/reoxygenation (H/R) injury of VECs. While the TIR/BB-loop mimetic (AS-1) disrupts the interaction between IL-1R and myeloid differentiation primary-response protein 88 (MyD88), its role in the VECs dysfunction under H/R is unclear. In this study, we first showed that there was an infiltration of inflammatory cells and the apoptosis of VECs by using a skin flap section from patients who received flap transplantation. We then showed that the H/R treatment induced apoptosis and loss of cell migration of endothelial cell line H926 were attenuated by AS-1. Furthermore, our data suggested that AS-1 inhibits the interaction between IL-1R and MyD88, and subsequent phosphorylation of IκB and p38 pathway, as well as the nuclear localization of NF-KB subunit p65/p50. Thus, this study indicated that the protective role of AS-1 in H/R induced cellular injury may be due to the AS-1 mediated down-regulation of IL-1R signaling pathway.
血管内皮细胞（VECs）的形态和功能异常是皮瓣缺血再灌注的危险因素。白细胞介素-1受体（IL-1R）介导的信号通路对VECs的缺氧/复氧（H/R）损伤至关重要。虽然TIR/BB环模拟物（AS-1）可破坏IL-1R与髓样分化初级反应蛋白88（MyD88）之间的相互作用，但其在H/R条件下对VECs功能障碍中的作用尚不清楚。在本研究中，我们首先通过使用接受皮瓣移植患者的皮瓣切片，证明了炎症细胞浸润和VECs凋亡的存在。然后我们发现，AS-1可减轻H/R处理诱导的内皮细胞系H926的凋亡和细胞迁移能力丧失。此外，我们的数据表明，AS-1可抑制IL-1R与MyD88之间的相互作用，以及随后IκB和p38通路的磷酸化，以及NF-κB亚基p65/p50的核定位。因此，本研究表明，AS-1在H/R诱导的细胞损伤中的保护作用可能归因于AS-1介导的IL-1R信号通路下调。
