Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
Inflammation. 2017 Oct;40(5):1532-1542. doi: 10.1007/s10753-017-0594-5.
Current treatments for ischemia-reperfusion (IR)-induced acute lung injury are limited. Mesenchymal stem cell-conditioned medium (CM) has been reported to attenuate lung injury. Neural crest stem cells (NCSCs), a type of multipotent stem cells, are more easily obtained than mesenchymal stem cells. We hypothesize that NCSC-CM has anti-inflammatory properties that could protect against IR-induced lung injury in rats. In this study, NCSC-CM was derived from rat NCSCs. Typical acute lung injury was induced by 30-min ischemia followed by 90-min reperfusion in adult male Sprague-Dawley rats. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to analyze the degree of lung injury after the experiment. NCSC-CM was administered before ischemia and after reperfusion. NCSC-CM treatment significantly attenuated IR-induced lung edema, as indicated by decreases in pulmonary vascular permeability, lung weight gain, wet to dry weight ratio, lung weight to body weight ratio, pulmonary arterial pressure, and protein level in BALF. The levels of tumor necrosis factor-α and interleukin-6 in the BALF were also significantly decreased. Additionally, NCSC-CM improved lung pathology and neutrophil infiltration in the lung tissue, and significantly suppressed nuclear factor (NF)-κB activity and IκB-α degradation in the lung. However, heating NCSC-CM eliminated these protective effects. Our experiment demonstrates that NCSC-CM treatment decreases IR-induced acute lung injury and that the protective mechanism may be attributable to the inhibition of NF-κB activation and the inflammatory response. Therefore, NCSC-CM may be a novel approach for treating IR-induced lung injury.
目前,缺血再灌注(IR)引起的急性肺损伤的治疗方法有限。间充质干细胞条件培养基(CM)已被报道可减轻肺损伤。神经嵴干细胞(NCSCs)是一种多能干细胞,比间充质干细胞更容易获得。我们假设 NCSC-CM 具有抗炎特性,可以防止大鼠 IR 引起的肺损伤。在这项研究中,NCSC-CM 是从大鼠 NCSCs 中提取的。典型的急性肺损伤是通过成年雄性 Sprague-Dawley 大鼠 30 分钟缺血后 90 分钟再灌注来诱导的。实验后收集支气管肺泡灌洗液(BALF)和肺组织,分析肺损伤程度。NCSC-CM 在缺血前和再灌注后给予。NCSC-CM 治疗显著减轻了 IR 引起的肺水肿,表现为肺血管通透性降低、肺重增加、湿重/干重比、肺重/体重比、肺动脉压和 BALF 中蛋白水平降低。BALF 中的肿瘤坏死因子-α和白细胞介素-6 水平也显著降低。此外,NCSC-CM 改善了肺组织的病理学和中性粒细胞浸润,并显著抑制了肺组织中核因子(NF)-κB 活性和 IκB-α的降解。然而,加热 NCSC-CM 消除了这些保护作用。我们的实验表明,NCSC-CM 治疗可减轻 IR 引起的急性肺损伤,其保护机制可能归因于 NF-κB 激活和炎症反应的抑制。因此,NCSC-CM 可能是治疗 IR 引起的肺损伤的一种新方法。