Many pathological conditions linked to cigarette smoking are caused by the production of reactive oxygen species (ROS). The present study was conducted to analyze the effect of ROS on the lungs of Swiss mice exposed to cigarette smoking, focusing on autophagy-mediated mechanisms, and investigate the involvement of SESN2, AMPK, and mTOR signaling. Mice were exposed to cigarette smoke (CS) for 7, 15, 30, 45, and 60 days; the control group was not exposed to CS. Only mice exposed to CS for 45 days were selected for subsequent N-acetylcysteine (NAC) supplementation and smoke cessation analyses. Exposure to CS increased the production of ROS and induced molecular changes in the autophagy pathway, including an increase in phosphorylated AMPK and ULK1, reduction in phosphorylated mTOR, and increases in SESN2, ATG12, and LC3B levels. NAC supplementation reduced ROS levels and reversed all molecular changes observed upon CS treatment, suggesting the involvement of oxidative stress in inducing autophagy upon CS exposure. When exposure to CS was stopped, there were decreases in the levels of oxidative stress, AMPK and ULK1 phosphorylation, and autophagy-initiating molecules and increase in mTOR phosphorylation. In conclusion, these results suggest the involvement of ROS, SESN2, AMPK, and mTOR in the CS-induced autophagic process in the lung.

许多与吸烟有关的病理状况是由活性氧 (ROS) 的产生引起的。本研究旨在分析 ROS 对暴露于吸烟的瑞士小鼠肺部的影响，重点关注自噬介导的机制，并研究 SESN2、AMPK 和 mTOR 信号传导的参与。小鼠暴露于香烟烟雾 (CS) 中 7、15、30、45 和 60 天；对照组不接触CS。仅选择暴露于 CS 45 天的小鼠进行后续N-乙酰半胱氨酸 (NAC) 补充剂和戒烟分析。暴露于 CS 会增加 ROS 的产生并诱导自噬途径中的分子变化，包括磷酸化 AMPK 和 ULK1 的增加、磷酸化 mTOR 的减少以及 SESN2、ATG12 和 LC3B 水平的增加。NAC 补充剂降低了 ROS 水平并逆转了在 CS 处理时观察到的所有分子变化，表明氧化应激参与了 CS 暴露后诱导自噬的作用。当停止接触 CS 时，氧化应激、AMPK 和 ULK1 磷酸化以及自噬起始分子的水平降低，mTOR 磷酸化增加。总之，这些结果表明 ROS、SESN2、AMPK 和 mTOR 参与了 CS 诱导的肺自噬过程。