@文章{Becq2100671，作者= {Becq, Fr{\'e}d{\'e}ric and Mirval, Sandra and Carrez, Thomas and L{\'e}v{\^e}que, Manuella and Billet, Arnaud and Coraux, Christelle and Sage, Edouard and Cantereau, Anne}，标题= {elexacaftor/tezacaftor/ivacaftor (Trikafta)在人类呼吸道上皮细胞中的拯救F508del-CFTR由于ivacaftor}的存在而被低估，volume = {59}， number = {2}， location-id = {2100671}， year = {2022}， doi = {10.1183/13993003.00671-2021}，作者:{欧洲呼吸学会}，摘188bet官网地址要:{Trikafta是目前治疗囊性纤维化(CF)的主要药物，已证明具有真正的临床效益。这种治疗是两种折叠校正器elexacaftor/tezacaftor (VX445/VX661)加上门控电位器ivacaftor (VX770)的三联疗法。在本研究中，我们的目的是比较F508del-CFTR在使用lumacaftor (VX809)、tezacaftor、elexacaftor、elexacaftor/tezacaftor与或不使用ivacaftor处理的细胞中的特性。我们通过Ussing chamber和全细胞膜片钳记录、Western blot和免疫定位实验研究了F508del-CFTR的功能、成熟和膜定位。通过人原代气道上皮细胞和表达F508del的细胞系CFBE和BHK，我们发现，elexacaftor/tezacaftor/ivacaftor组合在挽救F508del- cftr异常成熟、根尖膜位置和功能方面是有效的，而ivacaftor的存在限制了这些作用。与其他校正剂和未处理细胞相比，elexacaftor/tezacaftor/ivacaftor和elexacaftor/tezacaftor显著增加了基础F508del-CFTR短路电流，这一效应依赖于ivacaftor和cAMP。这些结果表明，基础的F508del-CFTR电流水平可能是CF细胞矫正效果的一个标志。当用ivacaftor联合任何校正剂处理细胞时，F508del-CFTR电流对随后急性添加的ivacaftor无反应，不像CFTR(囊性纤维化跨膜电导调节剂)增强剂染料根素和Cact-A1会增加elexacaftor/tezacaftor/ivacaftor和elexacaftor/tezacaftor校正的F508del-CFTR电流。这些结果表明ivacaftor降低了Trikafta的矫治效果。 Thus, combining elexacaftor/tezacaftor with a different potentiator might improve the therapeutic efficacy for treating CF patients.Ivacaftor is not able to potentiate the function of Trikafta-rescued F508del-CFTR due to its destabilising effect. Ivacaftor does not preclude the use of different potentiators combined with Trikafta, so the beneficial effect of Trikafta is underestimated. https://bit.ly/3dxlsJb}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/59/2/2100671}, eprint = {//www.qdcxjkg.com/content/59/2/2100671.full.pdf}, journal = {European Respiratory Journal} }