Department of Occupational and Environmental Health, Public Health School, Xinjiang Medical University, Urumqi 830000, China.
Department of Basic Nursing, Nursing School, Xinjiang Medical University, Urumqi 830000, China.
Biomed Res Int. 2021 Mar 1;2021:6685493. doi: 10.1155/2021/6685493. eCollection 2021.
The vascular injury induced by central venous catheter (CVC) indwelling is the basis for the occurrence and development of CVC-related complications, such as phlebitis, venous thrombosis, and catheter-related infections. Focal adhesion kinase (FAK) and FAK-protein kinase B (AKT) signaling pathway are of great significance in tissue repair after trauma. Here, we investigated the role and mechanism of the FAK inhibitor (1,2,4,5-phenyltetramine tetrahydrochloride (Y15)) in oxidative damage caused by CVC. EA.hy926 cells were divided into the control group (normal control), CVCs+scratches group (the intercepted CVC segments coculturing with scratched EA.hy926 cells), and CVCs+scratches+Y15 group (Y15 was added to the cell culture supernatant with CVCs + scratches at a final concentration of 50 mol·L). New Zealand rabbits were randomly divided into the control group (normal control), CVC group (CVC was inserted through the rabbit's right jugular vein to the junction of the right atrium and superior vena cava), and CVC+Y15 group (CVC was immersed in a 50 mol·L Y15 solutions before insertion). The levels of markers and proteins related to oxidative damage in cells, cell culture supernatant, serum, and external jugular vein were measured by commercial kits and western blot, respectively. We found that Y15 treatment significantly decreased ROS and MDA levels and increased cell viability, NO, and SOD levels in a time-dependent manner in rabbit serum and cell culture supernatant. In addition, Y15 effectively reduced the CVC-induced pathological changes of damaged vascular tissues. Y15 also downregulated the levels of p-FAK Tyr 397 and p-Akt Ser 473 in damaged external jugular vein and EA.hy926 cells. These findings suggest that Y15 alleviated CVC-induced oxidative damage to blood vessels by suppressing focal FAK-Akt pathway activation.
中心静脉导管（CVC）留置引起的血管损伤是 CVC 相关并发症发生和发展的基础，如静脉炎、静脉血栓形成和导管相关性感染。黏着斑激酶（FAK）和 FAK-蛋白激酶 B（AKT）信号通路在创伤后组织修复中具有重要意义。在这里，我们研究了 FAK 抑制剂（1,2,4,5-苯四胺四盐酸盐（Y15））在 CVC 引起的氧化损伤中的作用和机制。EA.hy926 细胞分为对照组（正常对照）、CVCs+划痕组（与划痕 EA.hy926 细胞共培养的截取 CVC 段）和 CVCs+划痕+Y15 组（在 CVCs+划痕的细胞培养上清液中加入终浓度为 50 μmol·L 的 Y15）。新西兰兔随机分为对照组（正常对照）、CVC 组（通过兔右颈静脉插入 CVC 至右心房和上腔静脉交界处）和 CVC+Y15 组（在插入前将 CVC 浸泡在 50 μmol·L 的 Y15 溶液中）。通过商业试剂盒和 Western blot 分别测量细胞、细胞培养上清液、血清和颈外静脉中与氧化损伤相关的标志物和蛋白水平。我们发现 Y15 处理可显著降低兔血清和细胞培养上清液中 ROS 和 MDA 水平，并呈时间依赖性增加细胞活力、NO 和 SOD 水平。此外，Y15 可有效减轻 CVC 引起的受损血管组织的病理变化。Y15 还下调了受损颈外静脉和 EA.hy926 细胞中 p-FAK Tyr 397 和 p-Akt Ser 473 的水平。这些发现表明，Y15 通过抑制焦点 FAK-Akt 通路的激活来减轻 CVC 引起的血管氧化损伤。
