Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China.
College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Anal Chim Acta. 2021 Jun 1;1162:338452. doi: 10.1016/j.aca.2021.338452. Epub 2021 Mar 27.
Airway smooth muscle (ASM) contraction is a major pathophysiological characteristic of asthma. Although β2-adrenoceptor (β2-AR) agonists are currently used as bronchodilators, they cause rapid effect and long-term agonist-induced desensitization. Thus, it is necessary to search for more effective and safer relaxant agents for ASM cells. In this work, bitter taste receptors (TAS2Rs) were demonstrated to be expressed in primary mouse ASM cells endogenously, and they were considered as new drug targets for asthma treatment. Traditional Chinese medicines (TCMs) contained a wide range of TAS2R agonists and some of them had the efficacy of relieving cough and asthma with less toxic side effects. Then the electronic cell-substrate impedance sensor (ECIS) was used for the first time to establish a method to detect the contraction/relaxation effects of ASM cells. Therefore, we introduced a biomimetic in vitro respiratory system using ASM cells on ECIS chips to screen for potential TCMs against asthma. Quinine, nobiletin, and picfeltarraenin IA screened in this study could effectively inhibit the ASM contraction in a concentration-dependent manner, showing potential value as novel anti-asthma drugs. Furthermore, the effective screening of anti-asthma drugs was realized based on 3D ASM cell arrays and gel imaging system. Consistent results were found and the reliability of the biomimetic in vitro respiratory system for the screening of TCMs against asthma was further verified. The biomimetic system designed in this study has the advantages of operation simplicity, high throughput, non-invasive, real-time, and high sensitivity, and therefore provides a promising drug screening platform for asthma disease.
气道平滑肌（ASM）收缩是哮喘的主要病理生理特征。虽然β2-肾上腺素能受体（β2-AR）激动剂目前被用作支气管扩张剂，但它们会引起快速作用和长期激动剂诱导的脱敏。因此，有必要寻找更有效和更安全的 ASM 细胞松弛剂。在这项工作中，内源性地证明苦味受体（TAS2R）在原代小鼠 ASM 细胞中表达，并且它们被认为是治疗哮喘的新药物靶点。中药（TCM）含有广泛的 TAS2R 激动剂，其中一些具有止咳和缓解哮喘的功效，且毒性副作用较小。然后，首次使用电子细胞-基底阻抗传感器（ECIS）建立了一种检测 ASM 细胞收缩/松弛作用的方法。因此，我们使用 ASM 细胞在 ECIS 芯片上引入了仿生体外呼吸系统，以筛选潜在的治疗哮喘的 TCM。本研究中筛选出的奎宁、诺必灵和皮克法他林 IA 能够以浓度依赖的方式有效抑制 ASM 收缩，显示出作为新型抗哮喘药物的潜在价值。此外，还基于 3D ASM 细胞阵列和凝胶成像系统实现了抗哮喘药物的有效筛选。发现了一致的结果，进一步验证了仿生体外呼吸系统筛选抗哮喘 TCM 的可靠性。本研究设计的仿生系统具有操作简单、高通量、非侵入性、实时和高灵敏度的优点，为哮喘疾病提供了有前途的药物筛选平台。
