Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, China.
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Respir Res. 2024 Mar 30;25(1):148. doi: 10.1186/s12931-024-02768-4.
Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms.
First, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments.
AXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1.
The present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.
虾青素（AXT）是一种酮式类胡萝卜素，具有多种生物学功能，包括抗氧化和抗纤维化作用。小气道重塑是慢性阻塞性肺疾病（COPD）的主要病理学特征，由上皮间质转化（EMT）和成纤维细胞分化增殖引起。目前仍缺乏有效的治疗方法。本研究旨在探讨 AXT 在 COPD 小气道重塑中的作用及其潜在机制。
首先，通过香烟烟雾（CS）暴露联合腹腔注射香烟烟雾提取物（CSE）建立 COPD 小鼠模型。采用苏木精-伊红（H&E）染色、免疫组织化学染色和 Western blot 检测 AXT 对 CS 联合 CSE 诱导的肺气肿、EMT 和小气道重塑的影响。此外，进一步通过体外实验探讨 AXT 对 CSE 诱导的 EMT 和成纤维细胞功能的影响。接下来，采用网络药理学分析 AXT 在 COPD 中的潜在作用靶点，以探讨 AXT 对 COPD 保护作用的具体机制。最后，通过分子对接和体外实验验证可能的机制。
AXT 减轻了 CS 联合 CSE 诱导的小鼠模型中的肺气肿、EMT 和小气道重塑。此外，AXT 抑制了气道细胞中的 EMT 过程和成纤维细胞的分化和增殖。机制上，AXT 通过直接结合并抑制 AKT1 的磷酸化来抑制成肌纤维细胞的激活。因此，我们的结果表明，AXT 通过抑制 AKT1 来防止小气道重塑。
本研究鉴定并阐明了 AXT 的一种新的食品功能，表明 AXT 可用于治疗 COPD 引起的小气道重塑。
