Institute of Physical Science and Information Technology, Anhui University, Hefei, 230601, People's Republic of China; Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
Department of Respiratory and Critical Care Diseases, 307 Hospital of PLA, Beijing, 100071, People's Republic of China.
Int Immunopharmacol. 2018 Oct;63:26-34. doi: 10.1016/j.intimp.2018.06.036. Epub 2018 Jul 29.
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) refer to acute and progressive hypoxic respiratory failure caused by non-cardiogenic factors, which is a common condition occurring in critically ill patients with widespread pulmonary inflammation. Use of a single medication or target cannot treat ALI/ARDS. Mesenchymal stem cells (MSCs) and FTY720, as an analogue of sphingosine-1-phosphate (S1P), can mitigate lipopolysaccharide (LPS)-induced inflammatory lung injury. In this investigation, the clinical efficacy of MSCs alone, FTY720 alone, and a MSC and FTY720 combination in the treatment of LPS-induced lung injury was evaluated in mouse models. The experimental results demonstrated that both MSCs and FTY720 alleviate lung injuries in mice. The combined application of MSCs and FTY720 yielded higher clinical efficacy in mitigating lung injuries compared with use of MSCs or FTY720 alone. Transcriptomic analysis was performed using an Agilent gene expression chip. By analyzing the differences in gene expression of lung tissues between treated and non-treated ALI/ARDS mice, Gene Ontology and Pathway terms related to ALI/ARDS treatment were identified. Moreover, the target genes which might play a pivotal role in the treatment of ALI/ARDS were also detected, thus providing a theoretical basis for multi-target or multi-drug combined treatment of ALI/ARDS and lay a solid foundation for clinical treatment of ALI/ARDS.
急性肺损伤和急性呼吸窘迫综合征(ALI/ARDS)是指由非心源性因素引起的急性进行性低氧性呼吸衰竭,是广泛肺部炎症的危重病患者常见的病症。单一药物或靶点的使用不能治疗 ALI/ARDS。间充质干细胞(MSCs)和 FTY720,作为鞘氨醇-1-磷酸(S1P)的类似物,可以减轻脂多糖(LPS)诱导的肺部炎症损伤。在本研究中,我们评估了 MSCs 单独、FTY720 单独以及 MSCs 和 FTY720 联合治疗 LPS 诱导的肺损伤在小鼠模型中的临床疗效。实验结果表明,MSCs 和 FTY720 均能减轻 LPS 诱导的肺损伤。与单独使用 MSCs 或 FTY720 相比,联合应用 MSCs 和 FTY720 能更有效地减轻肺损伤。使用 Agilent 基因表达芯片进行转录组分析。通过分析经治疗和未经治疗的 ALI/ARDS 小鼠肺组织之间基因表达的差异,确定了与 ALI/ARDS 治疗相关的基因本体论和途径术语。此外,还检测到可能在 ALI/ARDS 治疗中起关键作用的靶基因,为 ALI/ARDS 的多靶点或多药物联合治疗提供了理论依据,并为 ALI/ARDS 的临床治疗奠定了坚实的基础。