Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
Curr Mol Med. 2024;24(5):610-619. doi: 10.2174/1566524023666230406134640.
Radiation-induced pulmonary fibrosis (RIPF) is a long-term complication of thoracic radiotherapy without effective treatment available.
This study aimed to establish a RIPF mouse model and explore the therapeutic effects and mechanisms of recombinant human endostatin (Endostar).
C57BL/6 mice received a 16-Gy dose of X-rays to the whole thorax with or without the administration of Endostar for 24 weeks.
Radiation-induced body weight loss was partially attenuated by Endostar (P<0.05). Endostar significantly reduced alveolar inflammation (P<0.05) and pulmonary fibrosis (P<0.001), as indicated by a decrease in the expression levels of collagen I and collagen IV in lung tissue (both P<0.001). Angiogenesis (as shown by CD31 immunohistochemistry) was also decreased (P<0.01). In irradiated mice, Endostar inhibited the transforming growth factor-β1 (TGF-β1)/drosophila mothers against the decapentaplegic 3 (Smad3)/extracellular regulated protein kinases (ERK) signaling pathway (all P<0.05). In vitro, Endostar treatment decreased the radiation-induced expression of TGF-β1, vascular endothelial growth factor (VEGF), p-Smad3, and p-ERK in alveolar epithelial cells and vascular endothelial cells (all P<0.05).
Endostar could alleviate RIPF through decreased antiangiogenic activity and inhibition of the TGF-β1/Smad3/ERK pathway.
放射性肺纤维化（RIPF）是胸部放射治疗的一种长期并发症，目前尚无有效的治疗方法。
本研究旨在建立 RIPF 小鼠模型，并探讨重组人血管内皮抑制素（恩度）的治疗效果及作用机制。
采用 16Gy 全身单次 X 射线照射 C57BL/6 小鼠，照射后联合或不联合给予恩度 24 周。
恩度部分减轻了放射性体重下降（P<0.05）。恩度显著减轻了肺泡炎症（P<0.05）和肺纤维化（P<0.001），表现为肺组织中胶原 I 和胶原 IV 表达水平降低（均 P<0.001）。血管生成（通过 CD31 免疫组化染色显示）也减少（P<0.01）。在照射小鼠中，恩度抑制了转化生长因子-β1（TGF-β1）/drosophila mothers against the decapentaplegic 3（Smad3）/细胞外调节蛋白激酶（ERK）信号通路（均 P<0.05）。在体外，恩度处理降低了放射性诱导的肺泡上皮细胞和血管内皮细胞中 TGF-β1、血管内皮生长因子（VEGF）、p-Smad3 和 p-ERK 的表达（均 P<0.05）。
恩度通过降低抗血管生成活性和抑制 TGF-β1/Smad3/ERK 通路缓解 RIPF。
