Gu Quankuan, Wang Yunlong, Zhang Haichao, Yang Wei, Meng Xianglin, Zhao Mingyan
Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Heilongjiang Provincial Key Laboratory of Critical Care Medicine, Harbin, Heilongjiang Province, China.
PLoS One. 2025 Apr 29;20(4):e0315473. doi: 10.1371/journal.pone.0315473. eCollection 2025.
The aim of this research was to investigate if the mitochondria- targeting peptide SS-31 could serve as a protective measure against bleomycin-induced pulmonary fibrosis in mice.
Mice were split into four groups named CON group, SS-31 group, BLM group, and the BLM + SS-31 group. SS-31 (intraperitoneal injection, 5mg/Kg) was administered daily from the day prior to the experiment for the control and model groups. Mice were euthanized after 28 days of the experiment, following which blood, bronchoalveolar lavage fluid, and lung tissue were collected for analysis.
BLM caused a large decrease in body weight in mice. However, the intraperitoneal injection of SS-31 slowed down the body weight loss in the mice. It was observed through HE and Masson staining, immunohistochemistry, hydroxyproline detection, and fibrosis index measurement via Western blot that SS-31 could alleviate pulmonary fibrosis caused by BLM. Electron microscopy and ATP detection further suggested that SS-31 might help protect mitochondrial structure and function. It was also found that SS-31 could reduce reactive oxygen species and myeloperoxidase, thereby alleviating the reduction of antioxidant factor MPO and SOD, as well as diminishing the inflammatory factors TNF-α, IL-1 β, and IL-6.
The mitochondria-targeting drug SS-31 exhibited potential in mitigating bleomycin-induced pulmonary fibrosis, improving mitochondrial structural and functional damage, stabilizing the balance between oxidative and antioxidant systems, reducing inflammatory factor expression, and improving apoptosis in lung tissue.
本研究旨在探究线粒体靶向肽SS-31是否可作为一种针对博来霉素诱导的小鼠肺纤维化的保护措施。
将小鼠分为四组，分别命名为CON组、SS-31组、BLM组和BLM + SS-31组。从实验前一天开始，对对照组和模型组小鼠每日腹腔注射SS-31（5mg/Kg）。实验28天后对小鼠实施安乐死，随后采集血液、支气管肺泡灌洗液和肺组织进行分析。
博来霉素导致小鼠体重大幅下降。然而，腹腔注射SS-31减缓了小鼠体重的减轻。通过苏木精-伊红（HE）染色、马松（Masson）染色、免疫组织化学、羟脯氨酸检测以及蛋白质免疫印迹法检测纤维化指数，发现SS-31可减轻博来霉素所致的肺纤维化。电子显微镜检查和三磷酸腺苷（ATP）检测进一步表明，SS-31可能有助于保护线粒体结构和功能。还发现SS-31可降低活性氧和髓过氧化物酶水平，从而减轻抗氧化因子髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）的减少，并减少炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）。
线粒体靶向药物SS-31在减轻博来霉素诱导的肺纤维化、改善线粒体结构和功能损伤、稳定氧化与抗氧化系统之间的平衡、降低炎症因子表达以及改善肺组织细胞凋亡方面具有潜在作用。
