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Original Article
  |   1701_44-52.pdf
J Korean Soc Neonatol. May;17(1):44-52.
Copyright ⓒ 2010 The Korean Society of Neonatology Neonatal Medicine
Neonatal Rat Necrotizing Enterocolitis Model Adopting Oral Endotoxin and Hypoxia Exhibits Increased Apoptosis through Caspase-3 Activation
Yun Kyoung Lee, M.D.*, Ee-Kyung Kim, M.D.‡, Ji Eun Kim, M.D.†, Yoon Joo Kim, M.D.‡, Se Hyung Son, M.D.‡, Han-Suk Kim, M.D.‡
Department of Pediatrics*, Department of Pathology†, Seoul National University College of Medicine, Seoul, Department of Pediatrics‡, Seoul National University Children's Hospital, Seoul, Korea
Purpose : The aim of this study was to develop a model for necrotizing enterocolitis (NEC) in the neonatal rat using endotoxin and hypoxia, a plausible insult in a neonatal intensive care and to investigate the role of apoptosis as the underlying mechanism. Methods : Newborn rats were given oral endotoxin and intermittent 8% hypoxia±caspase inhibitor. The intestinal histology was evaluated using hematoxylin-eosin staining. Apoptosis was analyzed with TUNEL staining and by measuring the caspase 3 activity in the intestinal lysates. IEC-6 cells were assessed for apoptosis and the expression of Bax, Bcl-2, Fas and FasL was measured after treatment with endotoxin and hypoxia. Results : Oral endotoxin (5 mg/kg) and exposure to 8% hypoxia of 60-min duration twice induced human NEC-like lesions in the rat intestine. Intestinal tissue revealed increased apoptosis and caspase-3 activity. After caspase inhibitor treatment, the grades of both apoptosis and NEC were significantly reduced. IEC-6 cells exhibited increased apoptosis and caspase 3 activity after endotoxin and hypoxia treatment and significantly increased Bax/Bcl-2 ratio compared to control cells. Conclusion : This neonatal rat model of NEC which was induced by oral endotoxin and intermittent hypoxia showed increased apoptosis of intestinal epithelial cells that was mediated by caspase 3 activation. Our model has a advantage in the study of NEC because the use of much more clinically plausible insults may provide a suitable model for the investigation of its pathophysiology and therapeutic trials.
Keywords: Necrotizing enterocolitis, Endotoxin, Hypoxia, Apoptosis, Caspase-3
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