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<p>Intestinal obstruction is a common surgical emergency characterised by rapid progression and high mortality. However, the underlying mechanisms remain incompletely elucidated. Here, we show, by combining single-cell RNA sequencing with in vivo pharmacological modulation in male rats, the temporal dynamics of neutrophil extracellular traps (NETs) formation and their contribution to barrier dysfunction in incarcerated small-bowel obstruction. Profiling of 23,320 intestinal cells reveals pronounced neutrophil infiltration in late-stage obstruction (24.59% of total cells) and enables identification of a discrete “NETs-associated neutrophil subset (Neu_NETs)”. These Neu_NETs exhibit marked transcriptional enrichment of IL-17, NF-κB and TNF signalling pathways. Functional analyses demonstrate a time-dependent accumulation of NETs within obstructed segments that inversely correlates with the expression of intestinal tight junction proteins. In vivo administration of the PAD4 inhibitor Cl-amidine significantly attenuates NETs formation, ameliorates histopathological injury, and decreases local levels of IL-1β and TNF-α. Therefore, targeting NETs may represent a strategy for treating intestinal obstruction.</p>

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scRNA-seq analysis shows neutrophil extracellular traps as drivers of obstruction-induced intestinal damage in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月15日

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  • Zhanchuan Li,
  • Yongxin Ye,
  • Peng Wang,
  • Fei Long,
  • Yingyi Zhang,
  • Xunri Zheng,
  • Changwei Lin,
  • Xiaorong Li,
  • Yang Bai,
  • Yi Zhang

摘要

Intestinal obstruction is a common surgical emergency characterised by rapid progression and high mortality. However, the underlying mechanisms remain incompletely elucidated. Here, we show, by combining single-cell RNA sequencing with in vivo pharmacological modulation in male rats, the temporal dynamics of neutrophil extracellular traps (NETs) formation and their contribution to barrier dysfunction in incarcerated small-bowel obstruction. Profiling of 23,320 intestinal cells reveals pronounced neutrophil infiltration in late-stage obstruction (24.59% of total cells) and enables identification of a discrete “NETs-associated neutrophil subset (Neu_NETs)”. These Neu_NETs exhibit marked transcriptional enrichment of IL-17, NF-κB and TNF signalling pathways. Functional analyses demonstrate a time-dependent accumulation of NETs within obstructed segments that inversely correlates with the expression of intestinal tight junction proteins. In vivo administration of the PAD4 inhibitor Cl-amidine significantly attenuates NETs formation, ameliorates histopathological injury, and decreases local levels of IL-1β and TNF-α. Therefore, targeting NETs may represent a strategy for treating intestinal obstruction.