Background. Asthma airway remodeling is closely related to the abnormal migration of human airway smooth muscle cells (ASMCs), and vascular endothelial growth factor (VEGF) is involved in the pathophysiological process of asthma. This study aimed to investigate the effect of VEGF on ASMC migration through in vitro cell experiments and to intervene in ASMC migration with different asthma drugs and signaling pathway inhibitors to provide a basis for screening effective drugs for airway remodeling. Methods. The effect of VEGF on the proliferation of ASMCs was detected by the CCK-8 method, and the effect of VEGF on the migration of ASMCs was proven by scratch and transwell assays. Different asthma drugs and signaling pathway inhibitors were used to interfere with the migration of ASMCs. The number of migrating cells was compared between the intervention and nonintervention groups. Results. Our results showed that VEGF induction enhanced ASMC migration; pretreatment with the commonly used asthma drugs (salbutamol, budesonide, and ipratropium bromide) significantly attenuated VEGF-induced ASMC migration; and inhibitors SB203580, LY294002, and Y27632 blocked the VEGF-induced activation of p38 MAPK, PI3K, and ROCK signaling pathway targets in ASMCs and inhibited migration. Conclusion. This study shows that the current commonly used asthma drugs salbutamol, budesonide, and ipratropium have potential value in the treatment of airway remodeling, and the p38 MAPK, PI3K, and ROCK signaling pathway targets are involved in the VEGF-induced ASMC migration process. Signaling pathway inhibitor drugs may be a new way to treat asthma-induced airway remodeling in asthma patients in the future. However, the related mechanism and safety profile still need further research.

中文翻译：

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不同干预因素对血管内皮生长因子诱导的人气道平滑肌细胞迁移的影响

背景。哮喘气道重塑与人气道平滑肌细胞（ASMC）的异常迁移密切相关，血管内皮生长因子（VEGF）参与哮喘的病理生理过程。本研究旨在通过体外细胞实验探讨VEGF对ASMC迁移的影响，并利用不同哮喘药物和信号通路抑制剂干预ASMC迁移，为筛选有效的气道重塑药物提供依据。方法。采用CCK-8法检测VEGF对ASMC增殖的影响，并通过划痕实验和Transwell实验证明VEGF对ASMC迁移的影响。使用不同的哮喘药物和信号通路抑制剂来干扰ASMCs的迁移。比较干预组和非干预组之间的迁移细胞数量。结果。我们的结果表明 VEGF 诱导增强了 ASMC 迁移；使用常用的哮喘药物（沙丁胺醇、布地奈德和异丙托溴铵）进行预处理可显着减弱 VEGF 诱导的 ASMC 迁移；抑制剂 SB203580、LY294002 和 Y27632 阻断 VEGF 诱导的 ASMC 中 p38 MAPK、PI3K 和 ROCK 信号通路靶点的激活并抑制迁移。结论。本研究表明目前常用的哮喘药物沙丁胺醇、布地奈德、异丙托溴铵在治疗气道重塑方面具有潜在价值，p38 MAPK、PI3K、ROCK信号通路靶点参与VEGF诱导的ASMC迁移过程。信号通路抑制剂药物可能是未来治疗哮喘患者气道重塑的新方法。然而，相关机制和安全性仍需进一步研究。