Transcriptome analysis of chemically polarised rat macrophages: in search of target genes for ARDS therapy

Acute respiratory distress syndrome (ARDS) is a severe clinical manifestation of an acute lung injury (ALI), which is characterized by poor oxygenation and non-compliant or "stiff" lungs. Modern guidelines for the treatment of ARDS include only symptomatic therapy: ventilator support, prone positioning, sedation and medications to prevent movement, diuretic medication for excess liquid removing, extracorporeal membrane oxygenation (ECMO). Lack of the pathogenic ARDS treatment contributed to the actualization of the search for new therapeutic approaches. Cell therapy is one of such approaches which are now of great interest in the ARDS therapy. Macrophages are known to play a key role in the pathogenesis of ARDS. Depending on the stage of the disease, macrophages exhibiting pro-inflammatory (M1) and anti-inflammatory (M2) states. It has been suggested that the utilisation of M2 macrophages in the early stages of the disease may contribute to a positive disease outcome. The aim of this study was to induce an anti-inflammatory phenotype of macrophages by knockdown of genes selected on the basis of transcriptome analysis of chemically polarised macrophages.急性呼吸窘迫综合征（Acute respiratory distress syndrome, ARDS）是急性肺损伤（Acute lung injury, ALI）的严重临床表现，以氧合功能障碍、肺顺应性降低即“僵硬肺”为特征。当前ARDS临床治疗指南仅涵盖对症治疗手段：呼吸机支持、俯卧位通气、镇静与肌松药物、用于清除体内多余体液的利尿剂，以及体外膜肺氧合（Extracorporeal membrane oxygenation, ECMO）。由于目前尚无针对ARDS的病原学特效治疗方案，这促使学界加紧探索新型治疗策略。细胞疗法便是当前ARDS治疗领域备受关注的新型策略之一。已知巨噬细胞在ARDS的发病机制中发挥关键作用：根据疾病分期不同，巨噬细胞可呈现促炎表型（M1型）与抗炎表型（M2型）。已有研究表明，在疾病早期应用M2型巨噬细胞或可改善患者预后。本研究旨在通过敲低基于化学极化巨噬细胞转录组分析筛选得到的基因，诱导巨噬细胞向抗炎表型分化。