GLP-2 Administration Results in Increased Proliferation but Paradoxically an Adverse Outcome in a Juvenile Piglet Model of Short Bowel Syndrome
GLP-2 Administration Results in Increased Proliferation but Paradoxically an Adverse Outcome in a Juvenile Piglet Model of Short Bowel Syndrome
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GLP-2 给药导致短肠综合症幼年仔猪模型增殖增加，但矛盾的是产生不良结果
DOI：
10.1097/01.mpg.0000304449.46434.06
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发表时间：
2008
影响因子：
2.9
通讯作者：
J. Bines
中科院分区：
文献类型：
--
作者：
P. Pereira;Eva S Nagy;Sarah L. Thomas;Russell G. Taylor;Magdy Sourial;Monique C J Paris;J. Holst;P. Fuller;J. Bines
目的：本研究的目的是检查胰高血糖素样肽-2（GLP-2）给药对仔猪、幼年短肠综合征模型的影响。材料和方法：4周龄的仔猪进行假手术或75%小肠切除术。术后，仔猪接受聚合婴儿配方饲料或饲料和皮下人重组GLP-2（1600 μg/天，持续7天，此后800 μg/天）。在整个实验过程中监测食物摄入，每两周采集粪便和血清样品。仔猪处死后，从十二指肠、空肠、回肠和末端回肠获得组织，并用于形态和功能分析。结果如下：GLP-2处理后，假手术组和小肠切除组回肠中增殖和凋亡细胞数量显著增加（P < 0.05）。GLP-2给药导致假手术和小肠切除仔猪的体重增加、血清白蛋白和胰蛋白酶降低（与单独的聚合婴儿配方食品饮食相比，P < 0.001）。结论：这是我们所知的第一项研究，以检查GLP-2给药在青少年短肠综合征模型中的作用。与成年啮齿动物研究相反，GLP-2给药导致不良结局，包括增重能力降低;血清白蛋白、组织麦芽糖酶和蔗糖酶降低;绒毛萎缩。我们预计这些信息将对未来的儿科临床试验产生重要影响。
Objective: The objective of the present study was to examine the effect of glucagon-like peptide-2 (GLP-2) administration in a piglet, juvenile model of short bowel syndrome. Materials and Methods: Four-week-old piglets underwent either a sham operation or 75% small bowel resection. Postoperatively, piglets received either polymeric infant formula diet or the diet and subcutaneous human recombinant GLP-2 (1600 μg/day for 7 days, 800 μg/day thereafter). Food intake was monitored throughout the experiment, and stool and serum samples obtained fortnightly. After the piglets were killed, tissues were obtained from the duodenum, jejunum, ileum, and terminal ileum, and used for morphological and functional analysis. Results: Treatment with GLP-2 resulted in significantly increased numbers of proliferating and apoptotic cells in the ileum of sham and small bowel resection piglets (P < 0.05). GLP-2 administration resulted in decreased weight gain, serum albumin, and disaccharidases in both sham and small bowel resection piglets (P < 0.001 compared with polymeric infant formula diet alone). Conclusions: This is the first study to our knowledge to examine the effect of GLP-2 administration in a juvenile short bowel syndrome model. Contrary to adult rodent studies, administration of GLP-2 resulted in adverse outcomes including reduced ability to gain weight; decreased serum albumin, tissue maltase, and sucrase; and villous atrophy. We anticipate this information will have important implications for future paediatric clinical trials.
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小肠切除后的肠适应和肠上皮细胞凋亡与 p53 无关。
DOI：
10.1152/ajpgi.1999.277.3.g717
发表时间：
1999
期刊：
The American journal of physiology
影响因子：
--
作者：
Shin,CE;FalconeJr,RA;Kemp,CJ;Erwin,CR;Litvak,DA;Evers,BM;Warner,BW
通讯作者：
Warner,BW
DOI：
10.1152/ajpgi.2000.279.6.g1249
发表时间：
2000-12-01
影响因子：
4.5
作者：
Burrin, DG;Stoll, B;Sangild, PT
通讯作者：
Sangild, PT
DOI：
10.1152/ajpgi.00426.2005
发表时间：
2006-06-01
影响因子：
4.5
作者：
Tang, Yuzhu;Swietlicki, Elzbieta A.;Rubin, Deborah C.
通讯作者：
Rubin, Deborah C.
影响因子：
4.8
作者：
Burrin, DG;Stoll, B;Holst, JJ
通讯作者：
Holst, JJ
影响因子：
29.4
作者：
Guan, XF;Stoll, B;Burrin, DG
通讯作者：
Burrin, DG