PDF(Pubmed)
Abstract：
Chronic obstructive pulmonary disease (COPD) is considered a severe disease mitigating lung physiological functions with high mortality outcomes, insufficient therapy, and pathophysiology pathways which is still not fully understood. Mesenchymal stem cells (MSCs) derived from bone marrow play an important role in improving the function of organs suffering inflammation, oxidative stress, and immune reaction. It might also play a role in regenerative medicine, but that is still questionable. Additionally, Melatonin with its known antioxidative and anti-inflammatory impact is attracting attention nowadays as a useful treatment. We hypothesized that Melatonin may augment the effect of MSCs at the level of angiogenesis in COPD. In our study, the COPD model was established using cigarette smoking and lipopolysaccharide. The COPD rats were divided into four groups: COPD group, Melatonin-treated group, MSC-treated group, and combined treated group (Melatonin-MSCs). We found that COPD was accompanied by deterioration of pulmonary function tests in response to expiratory parameter affection more than inspiratory ones. This was associated with increased Hypoxia inducible factor-1α expression and vascular endothelial growth factor level. Consequently, there was increased CD31 expression indicating increased angiogenesis with massive enlargement of airspaces and thinning of alveolar septa with decreased mean radial alveolar count, in addition to, inflammatory cell infiltration and disruption of the bronchiolar epithelial wall with loss of cilia and blood vessel wall thickening. These findings were improved significantly when Melatonin and bone marrow-derived MSCs were used as a combined treatment proving the hypothesized target that Melatonin might augment MSCs aiming at vascular changes.
摘要：
慢性阻塞性肺疾病（COPD）被认为是一种严重的疾病，可缓解肺生理功能，死亡率高。治疗不足,和病理生理学途径仍未完全理解。骨髓间充质干细胞(MSCs)在改善炎症器官功能方面发挥重要作用,氧化应激，和免疫反应。它也可能在再生医学中发挥作用，但这仍然值得怀疑。此外,褪黑激素具有已知的抗氧化和抗炎作用，如今作为一种有用的治疗方法引起了人们的注意。我们假设褪黑素可能增强MSCs在COPD血管生成水平上的作用。在我们的研究中,使用吸烟和脂多糖建立COPD模型。将COPD大鼠分为四组:COPD组,褪黑素治疗组，MSC治疗组，和联合治疗组(褪黑素-MSCs)。我们发现，与吸气相比，COPD对呼气参数影响的反应更多，伴随着肺功能测试的恶化。这与缺氧诱导因子-1α表达和血管内皮生长因子水平升高有关。因此,CD31表达增加，表明血管生成增加，气道大量扩大，肺泡间隔变薄，平均放射状肺泡计数减少。此外,炎性细胞浸润和细支气管上皮壁破坏，纤毛丢失和血管壁增厚。当褪黑素和骨髓来源的MSCs用作联合治疗时，这些发现得到了显着改善，证明了假设的目标，即褪黑素可能会增强针对血管变化的MSCs。
