Neonatal Rat Necrotizing Enterocolitis Model Adopting Oral Endotoxin and Hypoxia Exhibits Increased Apoptosis through Caspase-3 Activation.
- Author:
Yun Kyoung LEE
1
;
Ee Kyung KIM
;
Ji Eun KIM
;
Yoon Joo KIM
;
Se Hyung SON
;
Han Suk KIM
;
Beyong Il KIM
;
Jung Hwan CHOI
Author Information
1. Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Necrotizing enterocolitis;
Endotoxin;
Hypoxia;
Apoptosis;
Caspase-3
- MeSH:
Animals;
Anoxia;
Apoptosis;
Caspase 3;
Enterocolitis, Necrotizing;
Epithelial Cells;
Humans;
Imidazoles;
In Situ Nick-End Labeling;
Infant, Newborn;
Intensive Care, Neonatal;
Intestines;
Nitro Compounds;
Rats
- From:Journal of the Korean Society of Neonatology
2010;17(1):44-52
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
