Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 44033, Republic of Korea.
Department of Pulmonary and Critical Care Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of Korea.
Oxid Med Cell Longev. 2022 Mar 20;2022:8200189. doi: 10.1155/2022/8200189. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause which leads to alveolar epithelial cell apoptosis followed by basement membrane disruption and accumulation of extracellular matrix, destroying the lung architecture. Oxidative stress is involved in the development of alveolar injury, inflammation, and fibrosis. Oxidative stress-mediated alveolar epithelial cell (AEC) apoptosis is suggested to be a key process in the pathogenesis of IPF. Therefore, the present study investigated whether grape seed proanthocyanidin extract (GSPE) could inhibit the development of pulmonary fibrosis via ameliorating epithelial apoptosis through the inhibition of oxidative stress. We found that GSPE significantly ameliorated the histological changes and the level of collagen deposition in bleomycin (BLM)-induced lungs. Moreover, GSPE attenuated lung inflammation by reducing the total number of cells in bronchoalveolar lavage (BAL) fluid and decreasing the expression of IL-6. We observed that the levels of HO leading to oxidative stress were increased following BLM instillation, which significantly decreased with GSPE treatment both and . These findings showed that GSPE attenuated BLM-induced epithelial apoptosis in the mouse lung and A549 alveolar epithelial cell through the inhibition of oxidative stress. Furthermore, GSPE could attenuate mitochondrial-associated cell apoptosis via decreasing the Bax/Bcl-2 ratio. The present study demonstrates that GSPE could ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibition of epithelial apoptosis through the inhibition of oxidative stress.
特发性肺纤维化（IPF）是一种原因不明的慢性、进行性间质性肺疾病，导致肺泡上皮细胞凋亡，随后基底膜破裂和细胞外基质积聚，破坏肺结构。氧化应激参与肺泡损伤、炎症和纤维化的发展。氧化应激介导的肺泡上皮细胞（AEC）凋亡被认为是 IPF 发病机制中的关键过程。因此，本研究探讨了葡萄籽原花青素提取物（GSPE）是否可以通过抑制氧化应激来改善上皮细胞凋亡，从而抑制肺纤维化的发展。我们发现，GSPE 可显著改善博莱霉素（BLM）诱导的肺组织学变化和胶原沉积水平。此外，GSPE 通过减少支气管肺泡灌洗液（BAL）中细胞总数和降低白细胞介素-6（IL-6）的表达来减轻肺炎症。我们观察到 BLM 注射后导致氧化应激的 HO 水平升高，而 GSPE 处理后显著降低。这些发现表明，GSPE 通过抑制氧化应激，减轻了 BLM 诱导的小鼠肺和 A549 肺泡上皮细胞中的上皮细胞凋亡。此外，GSPE 可以通过降低 Bax/Bcl-2 比值来减轻线粒体相关细胞凋亡。本研究表明，GSPE 可通过抑制氧化应激抑制上皮细胞凋亡，从而改善博莱霉素诱导的小鼠肺纤维化。
