PI3K/Akt signal pathway was blocked by Wortmannin, a specific inhibitor of phosphoinositide-3 kinase (PI3K), and the effects of intestinal trefoil factor (ITF) on PI3K and caspase-3/9 in newborn rats with necrotizing enterocolitis (NEC) were investigated to explore the protective mechanism of ITF against NEC. Experimental NEC was induced by exposure to hypoxia for 60 sec followed by cold stress at 4°C for 10 min. A total of 50 One-day-old Wistar rats were randomly divided into five groups : group A, NEC+NS; group B, NEC+ITF; group C,NEC+ wortmannin; group D ,NEC+ wortmannin + ITF; group E , Normal control. The animals were euthanized at development of NEC, and at 96 h the intestinal tissue was harvested and examined for histological changes of NEC, and then the PI3K content and Caspase-3/9 activity were detected using ELISA and spectrophotometry, respectively. The PI3K content (pg/ml) in group A was slightly higher than group E (P<0.05), and there was no significant difference between group A and D (P>0.05), but the PI3K content (pg/ml) in group B was significantly higher than the remaining groups (P<0.01), and the PI3K content (pg/ml) in group C was significantly lower compared with group E (P<0.01). Compared with group B and E, Caspase-3/9 activity was significantly higher in group A than in group B and E (P<0.01), but all lower than that in group C. So we concluded that ITF could activate the PI3K/Akt pathway to down-regulate Caspase-3/9 activity, and to protect against intestinal damage of NEC rats.
Key words: Intestinal trefoil factor, necrotizing enterocolitis, PI3K/Akt signal transduction, Caspase-9, Caspase-3.
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