新生儿高氧症诱导衰老的膜巨细胞中的代谢重编程,导致持续的肺损伤
Fanjie Lin1, Elena Pineda2,3, Bethany McGonnigal4
1State Key Laboratory of Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 510120 Guangzhou, Guangdong, China.
Frontiers in bioscience (Landmark edition)
|February 28, 2026
概括
新生儿高氧会导致肺细胞衰老,主要发生在巨细胞中. 针对这些衰老细胞使用老化药物可以减轻肺损伤,为支气管肺功能失调提供潜在的治疗策略.
科学领域:
- 肺部医学 肺部医学
- 新生儿科学 新生儿科学
- 细胞生物学 细胞生物学
背景情况:
- 支气管肺功能障碍症 (BPD) 是一种慢性肺部疾病,会影响早产婴儿.
- 在动物中,新生儿高氧暴露会诱导类似BPD的肺表型和细胞衰老.
- 衰老的肺巨细胞在高氧模型中占主导地位,在出生后的第7天达到顶峰 (pnd7).
研究的目的:
- 定义由新生儿高氧引起的衰老的肺巨的分子和功能特征.
- 研究这些衰老的巨细胞在肺损伤的发展和持久性中的作用.
- 为了评估治疗干预的目标老化的细胞在高氧诱导的肺损伤模型.
主要方法:
- 在新生儿高氧化症后,从衰老的肺细胞中重新分析scRNA-seq数据.
- 使用等级分类和手动注释识别和描述衰老的巨细胞集群.
- 在新生小鼠中使用二乙酸盐 (DCA) 和老化尾酒 (quercetin和dasatinib) 的体内验证.
主要成果:
- 巨细胞构成了65.90%的衰老细胞,确定了M1-样和状细胞表型.
- 衰老的巨细胞表现出改变的新陈代谢 (糖解,酸,谷氨酸路径) 和高调的先天免疫力/DNA损伤基因.
- 二乙酸盐 (DCA) 治疗减少了巨细胞衰老和肺损伤;老化尾酒减轻了持续的肺损伤.
结论:
- 新生儿高氧症诱导异质老化的巨细胞,具有代谢重编程和失调的信号传递.
- 这些衰老的巨细胞有助于肺损伤的发展和持续.
- 准衰老的巨细胞为BPD和相关的肺损伤提供了潜在的治疗途径.
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