Pediatric research · 2024
A neonatal mouse model of meconium peritonitis generated using human meconium slurry.
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Ashina Mariko, Kido Takumi, Shirai Keisuke, Masuda Yu, Imagawa Yukihito, Nakata Yuki, Nozu Kandai, Fujioka Kazumichi
Аннотация
BACKGROUND: Meconium peritonitis is a noninfectious chemical peritonitis that occurs following fetal intestinal perforation and leakage of meconium into the abdominal cavity. Because of the lack of appropriate animal models, its pathophysiology has not yet been elucidated. We aimed to create a neonatal mouse model of meconium peritonitis using human meconium slurry (MS).
METHODS: A stock MS solution prepared from fresh meconium obtained from healthy term infants was administered intraperitoneally to 4-d-old newborn mice. An MS LD40 was then administered, and changes in body weight, hematology, serum biochemistry, and immunomodulatory gene expression were determined. The MS was subjected to antibiotic treatment and heat inactivation to validate the content. Finally, comparisons with nonsurgical neonatal sepsis mouse models were performed.
RESULTS: Dose-dependent mortality rates were observed, with an LD40 of 200 µL/body weight established. Substantial hematological and hepatorenal abnormalities and increased inflammatory gene expression were observed. Although antibiotic treatment was ineffective, the survival rate was improved by enzymatic inactivation of MS. Importantly, the systemic responses to MS were distinct from those observed in neonatal sepsis model mice.
CONCLUSION: The MS model closely reflects the pathology of human neonatal meconium peritonitis and maybe useful in research elucidating the pathophysiology of this condition.
IMPACT: In this study, we generated a neonatal mouse model of meconium peritonitis through intraperitoneal administration of human meconium slurry. We clarified that the pathogenic agent in meconium slurry is mainly a digestive enzyme, and that the systemic responses elicited by meconium slurry were distinct from those in a neonatal sepsis mouse model. As our mouse model is simple and highly reproducible, it is useful for elucidating the pathophysiology of meconium peritonitis.
METHODS: A stock MS solution prepared from fresh meconium obtained from healthy term infants was administered intraperitoneally to 4-d-old newborn mice. An MS LD40 was then administered, and changes in body weight, hematology, serum biochemistry, and immunomodulatory gene expression were determined. The MS was subjected to antibiotic treatment and heat inactivation to validate the content. Finally, comparisons with nonsurgical neonatal sepsis mouse models were performed.
RESULTS: Dose-dependent mortality rates were observed, with an LD40 of 200 µL/body weight established. Substantial hematological and hepatorenal abnormalities and increased inflammatory gene expression were observed. Although antibiotic treatment was ineffective, the survival rate was improved by enzymatic inactivation of MS. Importantly, the systemic responses to MS were distinct from those observed in neonatal sepsis model mice.
CONCLUSION: The MS model closely reflects the pathology of human neonatal meconium peritonitis and maybe useful in research elucidating the pathophysiology of this condition.
IMPACT: In this study, we generated a neonatal mouse model of meconium peritonitis through intraperitoneal administration of human meconium slurry. We clarified that the pathogenic agent in meconium slurry is mainly a digestive enzyme, and that the systemic responses elicited by meconium slurry were distinct from those in a neonatal sepsis mouse model. As our mouse model is simple and highly reproducible, it is useful for elucidating the pathophysiology of meconium peritonitis.