Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
Department of respiration, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, People's Republic of China.
Sci Rep. 2017 Jan 24;7:41202. doi: 10.1038/srep41202.
Small-airway remodelling is one of the most remarkable pathological features of chronic obstructive pulmonary disease (COPD), in which angiogenesis plays a critical role that contributes to disease progression. The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF), as well as its receptors, VEGFR1, VEGFR2, are thought to be the major mediators of pathological angiogenesis, and sunitinib exhibits anti-angiogenesis property through VEGF blockage and has been widely used to treat various cancers. In our study, Sprague-Dawley rats were subjected to lipopolysaccharide (LPS) injection and cigarette smoke (CS) inhalation to induce COPD, following sunitinib administration was conducted. Haematoxylin-eosin, Masson staining and immunostaining analysis were used to evaluate the pathological changes; quantitative real-time PCR and enzyme-linked immunosorbent assay were performed to provide more compelling data on the function of VEGF, VEGFR1, VEGFR2 in angiogenesis. Sunitinib treatment was associated with less angiogenesis in small-airway remodelling with a slightly disordered lung architecture, and lower expression level of VEGF, VEGFR1, VEGFR2. Overall, our results indicate that VEGF is a vital important factor that contributes to the small-airway remodelling in a rat model of COPD through promoting angiogenesis, which mainly depend on the specific binding between VEGF and VEGFR1 and can be effectively attenuated by sunitinib.
小气道重塑是慢性阻塞性肺疾病（COPD）最显著的病理特征之一，其中血管生成起着关键作用，促进疾病进展。内皮细胞特异性有丝分裂原血管内皮生长因子（VEGF）及其受体 VEGFR1、VEGFR2 被认为是病理性血管生成的主要介质，而舒尼替尼通过阻断 VEGF 表现出抗血管生成特性，并已广泛用于治疗各种癌症。在我们的研究中，通过脂多糖（LPS）注射和香烟烟雾（CS）吸入使 Sprague-Dawley 大鼠诱导 COPD，随后进行舒尼替尼给药。苏木精-伊红、Masson 染色和免疫染色分析用于评估病理变化；实时定量 PCR 和酶联免疫吸附试验提供了更有说服力的数据，证明了 VEGF、VEGFR1、VEGFR2 在血管生成中的作用。舒尼替尼治疗与小气道重塑中的血管生成减少相关，小气道重塑伴有轻微紊乱的肺结构，VEGF、VEGFR1、VEGFR2 的表达水平降低。总体而言，我们的结果表明，VEGF 是通过促进血管生成导致 COPD 大鼠模型中小气道重塑的重要因素，这主要取决于 VEGF 与 VEGFR1 的特异性结合，并且可以通过舒尼替尼有效减弱。
