PPAR-gamma agonist protects against intestinal injury during necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) remains a lethal condition for many premature infants. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor family, has been shown to play a protective role in cellular inflammatory responses; however, its role in NEC is not clearly defined. We sought to examine the expression of PPAR-gamma in the intestine using an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-gamma agonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice were randomized to receive sham (control) or I/R injury to the gut induced by transient occlusion of superior mesenteric artery for 45 min with variable periods of reperfusion. I/R injury resulted in early induction of PPAR-gamma expression and activation of NF-kappaB in small intestine. Pretreatment with PPAR-gamma agonist, 15d-PGJ(2), attenuated intestinal NF-kappaB response and I/R-induced gut injury. Activation of PPAR-gamma demonstrated a protective effect on small bowel during I/R-induced gut injury.
Baregamian
Naira
N
Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0353, USA.
Mourot
Joshua M
JM
Ballard
Amie R
AR
Evers
B Mark
BM
Chung
Dai H
DH
D000818:Animals; D002460:Cell Line; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
C477819:15-deoxyprostaglandin J2; D016328:NF-kappa B; D047495:PPAR gamma; D015230:Prostaglandin D2