Effects of impaired glucocorticoid receptor function in hemorrhagic shock-induced lung injury with pre-existing cigarette smoke-induced chronic obstructive pulmonary disease (B07*)

糖皮质激素受体功能受损对失血性休克引起的肺损伤以及先前存在的香烟烟雾引起的慢性阻塞性肺病的影响 (B07*)

• 批准号: 414059960
• 金额: --
• 依托单位: Institut für Molekulare Endokrinologie der Tiere
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/414059960?language=en
• 关键词: Effects; impaired; glucocorticoid; receptor; function

When mice receive intensive care treatment, we found that a lack of GR dimerization (GRdim) increases mortality, aggravates hypotension, and further impairs lung function after challenge with lipopolysaccharides. Therefore, B07 N hypothesizes that lung injury and systemic inflammation after hemorrhagic shock are exacerbated in GRdim mice, which is further promoted by pre-traumatic cigarette smoke exposure-induced COPD. We expect that glucocorticoid (GC) treatment improves lung function and reduces inflammation through synergistic gene induction, which is promoted by inflammatory- and anti-inflammatory-acting signaling pathways dependent on GRdim in alternative macrophages.

当小鼠接受重症监护治疗时，我们发现缺乏GR二聚化（GRdim）会增加死亡率，加重低血压，并在脂多糖激发后进一步损害肺功能。因此，B07 N假设，在GRdim小鼠中，失血性休克后的肺损伤和全身炎症加剧，这进一步被创伤前香烟烟雾吸入诱导的COPD所促进。我们预计糖皮质激素（GC）治疗可以通过协同基因诱导来改善肺功能并减少炎症，而协同基因诱导是由替代巨噬细胞中依赖于GRdim的炎症和抗炎作用信号通路促进的。