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<p>NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase 1 (Caspase-1)/gasdermin D (GSDMD)-mediated pyroptosis is linked to spinal cord injury (SCI) pathogenesis. The levels of short-chain fatty acids (SCFAs), especially butyric acid, are significantly altered after SCI. Sodium butyrate (NaB) has anti-inflammatory effects on SCI; however, its effect on pyroptosis is unknown. The aim of this study was to determine the role of NaB in SCI functional recovery and its effect on NLRP3/Caspase-1/GSDMD-mediated pyroptosis.&#xa0;SCI model rats were established using aneurysm clips. After SCI, rats were administered NaB (300&#xa0;mg/kg) via gavage. SCFAs in faeces were measured using gas chromatography-mass spectrometry. Motor function recovery was assessed using cylinder rearing and grooming tests. Histopathological analysis was performed using haematoxylin-eosin staining, transmission electron microscopy, and terminal deoxynucleotidyl transferase dUTP nick-end labelling. The expression of proteins associated with pyroptosis signalling pathways was analysed using enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry.&#xa0;SCFAs levels, particularly butyric acid, significantly decreased after SCI. NaB treatment promoted forelimb motor function recovery and attenuated pathological SCI. NaB also decreased spinal pro-inflammatory factors (interleukin-18 and interleukin-1β) and downregulated pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein, Caspase-1, and GSDMD.&#xa0;NaB inhibits NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis and inflammation, exerting protective and therapeutic effects in SCI, suggesting NaB as an effective SCI treatment.</p> Graphical abstract <p></p>

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Sodium butyrate alleviates spinal cord injury via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月24日

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  • Yanru Cui,
  • Qiuyu Cen,
  • Jing Feng,
  • Juanfang Wei,
  • Linjie Wang,
  • Cong Chang,
  • Rizhao Pang,
  • Junyu Wang,
  • Anren Zhang

摘要

NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase 1 (Caspase-1)/gasdermin D (GSDMD)-mediated pyroptosis is linked to spinal cord injury (SCI) pathogenesis. The levels of short-chain fatty acids (SCFAs), especially butyric acid, are significantly altered after SCI. Sodium butyrate (NaB) has anti-inflammatory effects on SCI; however, its effect on pyroptosis is unknown. The aim of this study was to determine the role of NaB in SCI functional recovery and its effect on NLRP3/Caspase-1/GSDMD-mediated pyroptosis. SCI model rats were established using aneurysm clips. After SCI, rats were administered NaB (300 mg/kg) via gavage. SCFAs in faeces were measured using gas chromatography-mass spectrometry. Motor function recovery was assessed using cylinder rearing and grooming tests. Histopathological analysis was performed using haematoxylin-eosin staining, transmission electron microscopy, and terminal deoxynucleotidyl transferase dUTP nick-end labelling. The expression of proteins associated with pyroptosis signalling pathways was analysed using enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. SCFAs levels, particularly butyric acid, significantly decreased after SCI. NaB treatment promoted forelimb motor function recovery and attenuated pathological SCI. NaB also decreased spinal pro-inflammatory factors (interleukin-18 and interleukin-1β) and downregulated pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein, Caspase-1, and GSDMD. NaB inhibits NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis and inflammation, exerting protective and therapeutic effects in SCI, suggesting NaB as an effective SCI treatment.

Graphical abstract