Trefoil factor family peptide 3 prevents the development and promotes healing of ischemia-reperfusion injury in weanling rats

被引:25
作者
Carrasco, R
Pera, M
May, FEB
Westley, BR
Martinez, A
Morales, L
机构
[1] Hosp del Mar, Dept Surg, Colorectal Surg Unit, IMAS, Barcelona 08003, Spain
[2] Hosp St Joan de Deu, Dept Pediat Surg, Esplugues, Spain
[3] Univ Newcastle Upon Tyne, Royal Victoria Infirm, Dept Pathol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
[4] Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain
关键词
ischemia-reperfusion injury; necrotizing enterocolitis; trefoil factor family peptides;
D O I
10.1016/j.jpedsurg.2004.07.017
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Background/Purpose: Although the pathogenesis of necrotizing enterocolitis (NEC) is not completely defined, ischemia appears to be one of the most important causative factors. Trefoil factor family peptide 3 (TFF3) is a peptide normally expressed in the small bowel and colon and is involved in the maintenance and repair of mucosal integrity. The authors hypothesized that monomeric (TFF3 Ser(57)) and dimeric (TFF3 Cys(57)) recombinant TFF3 may prevent the development and accelerate healing of intestinal ischemia-reperfusion injury in weanling rats. Methods: Intestinal injury was induced in 18-day-old rats by occlusion of the superior mesenteric vessels for 60 minutes. To examine the protective effect, rats were given 3 mug/g of TFF3 Ser(57) or TFF3 Cys(57) by subcutaneous or enteral administration 30 minutes before the vascular occlusion. To examine the healing effect, rats were given 3 mug/g of TFF3 Ser(57) or TFF3 Cys(57) by subcutaneous or enteral administration 60 minutes after the beginning of reperfusion. Samples from small bowel and colon were collected for morphometric analysis after 3 hours of reperfusion. Mucosal damage was assessed by the Chiu score. Results: Both forms of TFF3 reduced the amount of damage when administered before the ischemia. Administration of TFF3 Ser(57) and TFF3 Cys(57) after the beginning of reperfusion significantly increased the villous height and decreased the Chiu score in the small intestine and colon. Conclusions: TFF3 Ser(57) monomer and TFF3 Cys(57) dimer prevent the development and promote healing of ischemia-reperfusion injury in weanling rats. There are no differences between the routes of administration of TFF3. (C) 2004 Elsevier Inc, All rights reserved.
引用
收藏
页码:1693 / 1700
页数:8
相关论文
共 33 条
[1]   EXPERIMENTAL ULCERATION LEADS TO SEQUENTIAL EXPRESSION OF SPASMOLYTIC POLYPEPTIDE, INTESTINAL TREFOIL FACTOR, EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA MESSENGER-RNAS IN RAT STOMACH [J].
ALISON, MR ;
CHINERY, R ;
POULSOM, R ;
ASHWOOD, P ;
LONGCROFT, JM ;
WRIGHT, NA .
JOURNAL OF PATHOLOGY, 1995, 175 (04) :405-414
[2]   Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats [J].
Babyatsky, MW ;
deBeaumont, M ;
Thim, L ;
Podolsky, DK .
GASTROENTEROLOGY, 1996, 110 (02) :489-497
[3]  
BALLANCE WA, 1990, J PEDIAT S, V117, P6
[4]  
BAUER CR, 1984, PEDIATRICS, V73, P682
[5]  
Beck PL, 1999, GASTROENTEROLOGY, V116, pA486
[6]   Homodimerization and hetero-oligomerization of the single-domain trefoil protein pNR-2/pS2 through cysteine 58 [J].
Chadwick, MP ;
Westley, BR ;
May, FEB .
BIOCHEMICAL JOURNAL, 1997, 327 :117-123
[7]  
CHIU CJ, 1970, ARCH SURG-CHICAGO, V101, P478
[8]   ANIMAL-MODELS OF NECROTIZING ENTEROCOLITIS [J].
CRISSINGER, KD .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 1995, 20 (01) :17-22
[9]   TREFOIL PEPTIDES PROMOTE EPITHELIAL MIGRATION THROUGH A TRANSFORMING GROWTH-FACTOR BETA-INDEPENDENT PATHWAY [J].
DIGNASS, A ;
LYNCHDEVANEY, K ;
KINDON, H ;
THIM, L ;
PODOLSKY, DK .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (01) :376-383
[10]   PREVENTION OF NECROTIZING ENTEROCOLITIS IN LOW-BIRTH-WEIGHT INFANTS BY IGA-IGG FEEDING [J].
EIBL, MM ;
WOLF, HM ;
FURNKRANZ, H ;
ROSENKRANZ, A .
NEW ENGLAND JOURNAL OF MEDICINE, 1988, 319 (01) :1-7