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KMID : 0438520100170010044
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Journal of the Korean Society of Neonatology
2010 Volume.17 No. 1 p.44 ~ p.52
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Neonatal Rat Necrotizing Enterocolitis Model Adopting Oral Endotoxin and Hypoxia Exhibits Increased Apoptosis
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Lee Yun-Kyoung
Kim Ee-Kyung
Kim Ji-Eun
Kim Yoon-Joo
Son Se-Kyung
Kim Han-Suk
Kim Beyong-Il
Choi Jung-Hwan
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Abstract
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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. (J Korean Soc Neonatol 2010;17:44-52)
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KEYWORD
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Necrotizing enterocolitis, Endotoxin, Hypoxia, Apoptosis, Caspase-3
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