Chen Zi-Yong, Ma Meng-Meng, Wang Rui, Zhang Qing-Qing, Xie Mei-Ling, Wang Ying-Li, Guo Yong-Xia, Liu Kui, Cao Li-Fang, He Feng-Lian, Fu Lin, Jiang Ya-Lin
The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, China.
Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, China.
Front Pharmacol. 2025 Apr 16;16:1552251. doi: 10.3389/fphar.2025.1552251. eCollection 2025.
Idiopathic pulmonary fibrosis (IPF) has a higher morbidity and poor prognosis. Gui-Zhi-Fu-Ling-Wan (GFW) is a traditional Chinese herbal formula which exerts anti-inflammatory and anti-oxidative effects. The goal was to determine the protective effect of GFW on bleomycin (BLM)-induced pulmonary fibrosis.
One hundred and twenty-four mice were randomly divided into eight groups, and orally supplemented with GFW (1 g/kg) in 1 week ago and continuing to 1 week later of single BLM intratracheal injection (5.0 mg/kg). Lung tissues were collected in 7 days and 21 days after BLM injection. BEAS-2B cells were pretreated with GFW (100 μg/mL) for three consecutive days before BLM (10 μg/mL) exposure. Cells were harvested in 12 or 24 h after BLM co-culture.
GFW supplementation alleviated BLM-induced alveolar structure destruction and inflammatory cell infiltration in mice lungs. BLM-incurred collagen deposition was attenuated by GFW. In addition, GFW pretreatment repressed BLM-evoked downregulation of E-cadherin, and elevation of N-cadherin and Vimentin in mouse lungs. Besides, BLM-excited GPX4 reduction, ferritin increases, lipid peroxidation, and free iron overload were significantly relieved by GFW pretreatment in mouse lungs and BEAS-2B cells. Notably, BLM-provoked mitochondrial reactive oxygen species (mtROS) excessive production, elevation of mitochondrial stress markers, such as HSP70 and CLPP, and mitochondrial injury, were all abolished in mouse lungs and BEAS-2B cells by GFW pretreatment.
GFW supplementation attenuated BLM-evoked lung injury and pulmonary fibrosis partially through repressing EMT and mtROS-mediated ferroptosis in pulmonary epithelial cells.
特发性肺纤维化（IPF）发病率较高且预后较差。桂枝茯苓丸（GFW）是一种具有抗炎和抗氧化作用的传统中药配方。本研究旨在确定GFW对博来霉素（BLM）诱导的肺纤维化的保护作用。
124只小鼠随机分为八组，在单次气管内注射BLM（5.0mg/kg）前1周口服给予GFW（1g/kg），并持续至注射后1周。在BLM注射后7天和21天收集肺组织。BEAS-2B细胞在暴露于BLM（10μg/mL）前连续三天用GFW（100μg/mL）预处理。在与BLM共培养12或24小时后收获细胞。
补充GFW减轻了BLM诱导的小鼠肺组织肺泡结构破坏和炎性细胞浸润。GFW减轻了BLM引起的胶原沉积。此外，GFW预处理抑制了BLM引起的小鼠肺组织中E-钙黏蛋白的下调以及N-钙黏蛋白和波形蛋白的升高。此外，GFW预处理显著减轻了BLM引起的小鼠肺组织和BEAS-2B细胞中谷胱甘肽过氧化物酶4（GPX4）的降低、铁蛋白的增加、脂质过氧化和游离铁过载。值得注意的是，GFW预处理消除了BLM引起的小鼠肺组织和BEAS-2B细胞中线粒体活性氧（mtROS）的过量产生、线粒体应激标志物如热休克蛋白70（HSP70）和线粒体基质加工肽酶（CLPP）的升高以及线粒体损伤。
补充GFW部分通过抑制肺上皮细胞中的上皮-间质转化（EMT）和mtROS介导的铁死亡减轻了BLM引起的肺损伤和肺纤维化。
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