State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 501 Haike Road, Shanghai 201203, China.
School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China.
Molecules. 2021 Mar 19;26(6):1715. doi: 10.3390/molecules26061715.
Pulmonary fibrosis is a severe and irreversible interstitial pulmonary disease with high mortality and few treatments. Magnesium lithospermate B (MLB) is a hydrosoluble component of and has been reported to have antifibrotic effects in other forms of tissue fibrosis. In this research, we studied the effects of MLB on pulmonary fibrosis and the underlying mechanisms. Our results indicated that MLB treatment (50 mg/kg) for seven days could attenuate bleomycin (BLM)-induced pulmonary fibrosis by reducing the alveolar structure disruption and collagen deposition in the C57 mouse model. MLB was also found to inhibit transforming growth factor-beta (TGF-β)-stimulated myofibroblastic transdifferentiation of human lung fibroblast cell line (MRC-5) cells and collagen production by human type II alveolar epithelial cell line (A549) cells, mainly by decreasing the expression of TGF-β receptor I (TGF-βRI) and regulating the TGF-β/Smad pathway. Further studies confirmed that the molecular mechanisms of MLB in BLM-induced pulmonary fibrosis mice were similar to those observed in vitro. In summary, our results demonstrated that MLB could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that MLB has great potential for pulmonary fibrosis treatment.
肺纤维化是一种严重且不可逆转的间质性肺疾病，死亡率高，治疗方法有限。丹参素镁 B（MLB）是丹参的一种水溶性成分，已被报道在其他形式的组织纤维化中具有抗纤维化作用。在这项研究中，我们研究了 MLB 对肺纤维化的影响及其潜在机制。我们的结果表明，MLB 治疗（50mg/kg）7 天可通过减少肺泡结构破坏和胶原沉积来减轻博来霉素（BLM）诱导的肺纤维化在 C57 小鼠模型中。MLB 还被发现可抑制转化生长因子-β（TGF-β）刺激的人肺成纤维细胞系（MRC-5）细胞的肌成纤维细胞转分化和人 II 型肺泡上皮细胞系（A549）细胞的胶原产生，主要通过降低 TGF-β受体 I（TGF-βRI）的表达并调节 TGF-β/Smad 通路。进一步的研究证实，MLB 在 BLM 诱导的肺纤维化小鼠中的分子机制与在体外观察到的相似。总之，我们的结果表明，MLB 可以在体内和体外减轻实验性肺纤维化，这表明 MLB 具有治疗肺纤维化的巨大潜力。
