吸烟是慢性炎症性疾病，如慢性阻塞性肺疾病（COPD）的主要原因。开发药物干预和递送策略以对抗与吸烟相关的COPD氧化应激非常重要。本研究在Wistar大鼠中通过纳米乳化剂中的半胱氨酸来对抗与吸烟烟雾（CS）相关的微环境。在体内，使用Wistar大鼠建立了经过28天CS处理和15天半胱氨酸纳米乳化剂治疗（从第29天开始，包括口服和吸入途径）。此外，我们利用人支气管上皮细胞系（BEAS2B）细胞系使用5% CS提取物进行了体外炎症和上皮-间质转化（EMT）研究。通过测定支气管肺泡灌洗液（BALF）中炎症和抗炎标记物，如肿瘤坏死因子-alpha（TNF-α），白细胞介素（IL）-6，IL-1β，IL-8，IL-10和IL-13，以评估半胱氨酸纳米乳化剂对疾病情况的规范化作用。肺泡和气管的组织病理学分析显示了畸变的肺实质和纤毛上皮屏障。为了获得关于COPD大鼠模型的机制洞察，利用高分辨质谱法对肺组织进行了“shotgun”蛋白质组学分析，发现ABI1，PPP3CA，PSMA2，FBLN5，ACTG1，CSNK2A1和ECM1等基因在所有组中存在显著差异。途径分析显示，自噬、受体酪氨酸激酶信号转导、细胞因子信号转导，细胞外基质组织和止血等是所有研究组主要贡献的途径。本研究提供了有关半胱氨酸经口或吸入预防CS诱导的氧化应激的新的临床前研究结果。

Cigarette smoking is the major cause of chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It is paramount to develop pharmacological interventions and delivery strategies against the cigarette smoke (CS) associated oxidative stress in COPD. This study in Wistar rats examined cysteamine in nanoemulsions to counteract the CS distressed microenvironment. In vivo, 28 days of CS and 15 days of cysteamine nanoemulsions treatment starting on 29th day consisting of oral and inhalation routes were established in Wistar rats. In addition, we conducted inflammatory and epithelial-to-mesenchymal transition (EMT) studies in vitro in human bronchial epithelial cell lines (BEAS2B) using 5% CS extract. Inflammatory and anti-inflammatory markers, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-8, IL-10, and IL-13, have been quantified in bronchoalveolar lavage fluid (BALF) to evaluate the effects of the cysteamine nanoemulsions in normalizing the diseased condition. Histopathological analysis of the alveoli and the trachea showed the distorted, lung parenchyma and ciliated epithelial barrier, respectively. To obtain mechanistic insights into the CS COPD rat model, "shotgun" proteomics of the lung tissues have been carried out using high-resolution mass spectrometry wherein genes such as ABI1, PPP3CA, PSMA2, FBLN5, ACTG1, CSNK2A1, and ECM1 exhibited significant differences across all the groups. Pathway analysis showed autophagy, signaling by receptor tyrosine kinase, cytokine signaling in immune system, extracellular matrix organization, and hemostasis, as the major contributing pathways across all the studied groups. This work offers new preclinical findings on how cysteamine taken orally or inhaled can combat CS-induced oxidative stress.