Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats.
OBJECTIVE
To investigate the dynamic change and role of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in neonatal rat with intestinal injury and to define whether necrotizing enterocolitis (NEC) is associated with the levels of nitric oxide synthase (NOS) in the mucosa of the affected intestine tissue.


METHODS
Wistar rats less than 24 h in age received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileum tissues were collected at 1, 3, 6, 12 and 24 h following LPS challenge for histological evaluation of NEC and for measurements of nNOS and iNOS. The correlation between the degree of intestinal injury and levels of NOS was determined.


RESULTS
The LPS-injected pups showed a significant increase in injury scores versus the control. The expression of nNOS protein and mRNA was diminished after LPS injection. There was a negative significant correlation between the nNOS protein and the grade of median intestinal injury within 24 h. The expression of iNOS protein and mRNA was significantly increased in the peak of intestinal injury.


CONCLUSIONS
nNOS and iNOS play different roles in LPS-induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of NOS inhibitors in NEC.
Lu
Hui
H
Department of Pediatrics, the Second Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China. luhui6699@sina.com
Zhu
Bing
B
Xue
Xin-Dong
XD
D000818:Animals; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D008070:Lipopolysaccharides; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II