Frontiers in Pharmacology (Sep 2024)

Paving the way ahead: protocol optimization of mouse models in crush syndrome related acute kidney injury research

  • Ou Qiao,
  • Ou Qiao,
  • Ou Qiao,
  • Ou Qiao,
  • Xinyue Wang,
  • Xinyue Wang,
  • Xinyue Wang,
  • Xinyue Wang,
  • Zizheng Li,
  • Zizheng Li,
  • Zizheng Li,
  • Zizheng Li,
  • Lu Han,
  • Lu Han,
  • Lu Han,
  • Lu Han,
  • Xin Chen,
  • Xin Chen,
  • Xin Chen,
  • Xin Chen,
  • Li Zhang,
  • Li Zhang,
  • Li Zhang,
  • Li Zhang,
  • Fengjiao Bao,
  • Fengjiao Bao,
  • Fengjiao Bao,
  • Fengjiao Bao,
  • Herui Hao,
  • Herui Hao,
  • Herui Hao,
  • Herui Hao,
  • Yingjie Hou,
  • Yingjie Hou,
  • Yingjie Hou,
  • Yingjie Hou,
  • Xiaohong Duan,
  • Xiaohong Duan,
  • Xiaohong Duan,
  • Xiaohong Duan,
  • Sania Saeed,
  • Sania Saeed,
  • Sania Saeed,
  • Sania Saeed,
  • Ning Li,
  • Ning Li,
  • Ning Li,
  • Ning Li,
  • Yanhua Gong,
  • Yanhua Gong,
  • Yanhua Gong,
  • Yanhua Gong

DOI
https://doi.org/10.3389/fphar.2024.1438127
Journal volume & issue
Vol. 15

Abstract

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BackgroundsCrush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures.MethodsMice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols.ResultsThe results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state.ConclusionWe successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI.

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