Vandetanib 作为治疗哮喘的前瞻性抗炎和抗收缩剂
2024/06/26
摘要
背景：Vandetanib是一种小分子酪氨酸激酶抑制剂。它主要通过抑制血管内皮生长因子受体 2 在一系列肺癌中发挥其治疗作用。然而，目前尚不清楚vandetanib是否对其他肺部疾病（尤其是哮喘）具有治疗作用。
目的：本研究探索了vandetanib在治疗哮喘中的开创性应用。
方法：体内实验（包括哮喘模型的建立，气道阻力测量和组织学分析）主要用于证实vandetanib的抗收缩和抗炎作用，而体外实验（包括肌肉张力测量和全细胞膜片钳记录）用于探索潜在的分子机制。
结果：在哮喘小鼠模型中的体内实验表明，vandetanib可以显著减轻全身炎症和一系列气道病理变化，包括超敏反应，高分泌和重塑。随后的体外实验表明，vandetanib能够通过钙动员来舒张小鼠气管的预收缩环，钙动员受特定离子通道（包括VDLCC，NSCC，NCX和K（+）通道）的调节。
结论：总之，我们的研究表明，vandetanib在哮喘治疗中具有抗收缩和抗炎特性，这也表明使用vandetanib通过减少异常气道收缩和全身炎症来治疗哮喘的可行性。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Front Pharmacol 2024;15(0):1345070；doi: 10.3389/fphar.2024.1345070. IF: 4.225)
Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma.
Xiaoyue, Zeng; Lu, Xue; Wei, Li;
Abstrast
Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma.
Objective：The present study investigated the pioneering use of vandetanib in the treatment of asthma.
Methods: In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism.
Results: In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels.
Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.
背景：Vandetanib是一种小分子酪氨酸激酶抑制剂。它主要通过抑制血管内皮生长因子受体 2 在一系列肺癌中发挥其治疗作用。然而，目前尚不清楚vandetanib是否对其他肺部疾病（尤其是哮喘）具有治疗作用。
目的：本研究探索了vandetanib在治疗哮喘中的开创性应用。
方法：体内实验（包括哮喘模型的建立，气道阻力测量和组织学分析）主要用于证实vandetanib的抗收缩和抗炎作用，而体外实验（包括肌肉张力测量和全细胞膜片钳记录）用于探索潜在的分子机制。
结果：在哮喘小鼠模型中的体内实验表明，vandetanib可以显著减轻全身炎症和一系列气道病理变化，包括超敏反应，高分泌和重塑。随后的体外实验表明，vandetanib能够通过钙动员来舒张小鼠气管的预收缩环，钙动员受特定离子通道（包括VDLCC，NSCC，NCX和K（+）通道）的调节。
结论：总之，我们的研究表明，vandetanib在哮喘治疗中具有抗收缩和抗炎特性，这也表明使用vandetanib通过减少异常气道收缩和全身炎症来治疗哮喘的可行性。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Front Pharmacol 2024;15(0):1345070；doi: 10.3389/fphar.2024.1345070. IF: 4.225)
Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma.
Xiaoyue, Zeng; Lu, Xue; Wei, Li;
Abstrast
Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma.
Objective：The present study investigated the pioneering use of vandetanib in the treatment of asthma.
Methods: In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism.
Results: In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels.
Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.
