Department of Respiratory Medicine, Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315010, China.
The Fist Ward, Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China.
Comput Intell Neurosci. 2022 Jul 18;2022:3564871. doi: 10.1155/2022/3564871. eCollection 2022.
A variety of internal and external lung diseases may eventually lead to pulmonary fibrosis, and insufficient autophagy is closely related to pulmonary fibrosis. This research is aimed to explore the mechanism of autophagy to alleviate pulmonary fibrosis. Then, a mouse model of pulmonary fibrosis induced by boromycin and histopathological lesions of the lungs of mice were observed by HE staining, which Masson staining assessed the degree of fibrosis in the lung tissue by detecting the expression of hydroxyproline in the tissue. RT-qPCR and western blotting were used to detect the levels of autophagy and Keap1/Nrf2 signaling pathway-related proteins. It was proved that autophagy-related proteins MAP1LC3(LC3) and Beclin 1 were decreased in mice with pulmonary fibrosis, while the expression of p62 was increased. Mice with pulmonary fibrosis worsened after injection of a 3-MA autophagy inhibitor, while injection of autophagy activation of rapamycin agent promoted Nrf2 nuclear mobilization. In a word, autophagy relieves pulmonary fibrosis through the activation of the Keap1/Nrf2 signaling pathway.
多种内、外源性肺疾病最终均可导致肺纤维化,而自噬不足与肺纤维化的发生密切相关。本研究旨在探讨自噬缓解肺纤维化的作用机制。然后,通过 HE 染色观察博来霉素诱导的肺纤维化小鼠模型和小鼠肺组织的组织病理学损伤,通过检测组织中羟脯氨酸的表达来评估 Masson 染色肺组织纤维化程度。采用 RT-qPCR 和 Western blot 检测自噬和 Keap1/Nrf2 信号通路相关蛋白的水平。结果证明,肺纤维化小鼠的自噬相关蛋白 MAP1LC3(LC3)和 Beclin 1 减少,而 p62 的表达增加。肺纤维化小鼠注射自噬抑制剂 3-MA 后病情恶化,而注射自噬激活剂雷帕霉素则促进了 Nrf2 的核转位。总之,自噬通过激活 Keap1/Nrf2 信号通路缓解肺纤维化。