课题背景：目前小肠移植排斥反应随着排斥免疫和抗排斥药物研究的深入已得到了较大的突破，小肠移植的功能恢复将成为其重点研究方向。胰高血糖素样肽2是新近发现的肠上皮生长因子，与以往发现的生长因子不同，具有肠道特异性促生长作用。

应用要点：实验在小肠移植后应用胰高血糖素样肽2，证实胰高血糖素样肽2有利于移植肠黏膜的再生和修复，进而促进肠功能的恢复，为治疗小肠移植术后移植肠功能低下提供了新的思路和方法。

同行评价；文章针对小肠移植后的功能恢复，应用胰高血糖素样肽2进行实验，结果表明胰高血糖素样肽2对移植小肠肠黏膜功能恢复具有促进作用。选题先进，设计合理，具有一定的临床应用价值。

摘要

背景：胰高血糖素样肽2是新近发现的肠上皮生长因子，具有肠道特异性的促生长作用。
目的：实验拟进一步验证胰高血糖素样肽2对小肠原位移植大鼠小肠结构和功能恢复的促进作用。
设计、时间及地点：随机对照动物实验，于2005-08/2006-09在大连医科大学生理教研室完成。
材料：将75只Wistar大鼠按随机数字表法分成3组，小肠移植组30只（供、受体各15只），胰高血糖素样肽2组30只（供、受体各15只），假手术组15只。
方法：小肠移植组及胰高血糖素样肽2组大鼠采用改良的kort法行2步法原位小肠移植；假手术组仅行开关腹手术。胰高血糖素样肽2组小肠移植后给予胰高血糖素样肽2以250 μg/（kg?d）分2次皮下注射，间隔12 h，连续给3 d。
主要观察指标：术后2 周用免疫组化法检测增殖细胞核抗原，并行肠黏膜组织病理学检查；分别于术后2，4，8 周检测移植小肠功能酶（Na+，K+-ATP酶、双糖酶）活性。
结果：①术后2 周胰高血糖素样肽2组肠黏膜绒毛高度、隐窝深度均高于小肠移植组，增殖细胞核抗原表达水平高于小肠移植组。②小肠移植组肠黏膜功能酶活性在术后2周下降明显，术后4周双糖酶活性恢复正常，术后8周Na+，K+-ATP酶活性也接近正常。胰高血糖素样肽2组术后2周时双糖酶活性恢复正常，术后4周时Na+，K+-ATP酶活性恢复正常。
结论：外源性胰高血糖素样肽2能促进原位移植小肠结构和功能的恢复。
关键词：小肠/移植；胰高血糖素；肠吸收；组织移植

朱亮，宫德正，邹原，李幼生，吴云红，袁博，关莉莉，吴琼，高子淇，刘立娇.胰高血糖素样肽2对移植小肠结构和功能恢复的作用[J].中国组织工程研究与临床康复，2008，12(18):3401-3405
[www.zglckf.com/zglckf/ejournal/upfiles/08-18/18/k-3401(ps).pdf]

Effects of glucagon-like peptide-2 on the recovery of structure and function of small intestinal following orthotopic transplantation

Abstract

BACKGROUND:Glucagon-like peptide-2 (GLP-2) is a newly found enteric epithelium growth factor and has intestinal tract specific growth promotion effect.
OBJECTIVE: To explore the promotive influence of GLP-2 on the recovery of structure and function of orthotopic intestinal transplantation in rats.
DESIGN, TIME AND SETTING: A randomized control animal experiment was performed at the Department of Pathology, Dalian Medical University from August 2005 to September 2006.
MATERIALS: Totally 75 Wistar rats were randomly divided into 3 groups: an orthotopic intestine transplantation group (15 donors and 15 receptors), a GLP-2 group (15 donors and 15 receptors) and a sham operation group (n=15).
METHODS: Two-step orthotopic intestinal transplantation (OIT) using modified Kort’s method was used in the orthotopic intestine transplantation and GLP-2 groups. Rats in the sham operation group only received open and close abdomen operation. GLP-2 (250 μg/kg) was subcutaneously injected into rats in the GLP-2 group after orthotopic intestine transplantation, twice a day, with an interval of 12 hours, successively for 3 days.
MAIN OUTCOME MEASURES: Two weeks after transplantation, immunohistochemistry was used to measure proliferating cell nuclear antigen. Pathology of intestinal mucosa was performed. Two, four and eight weeks after surgery, intestinal mucosal functional enzyme activity (disaccharides, Na+/K+-ATPase) was detected.
RESULTS: Two weeks after surgery, intestinal mucosal height and recessus depth were higher in the GLP-2 group than in the orthotopic intestine transplantation group. Proliferating cell nuclear antigen expression was higher compared to the orthotopic intestine transplantation group. Intestinal mucosal functional enzyme activity significantly decreased in the orthotopic intestine transplantation group at week after surgery. Activity of disaccharides returned to baseline at 4 weeks and mucosal Na+/K+-ATPase activity returned to baseline at 8 weeks. In the GLP-2 group, disaccharides activity returned to baseline at 2 weeks and mucosal Na+/K+-ATPase activity returned to baseline at 4 weeks.
CONCLUSION: GLP-2 supplementation can promote recovery of structure and function of intestine following orthotopic transplantation.

Zhu L, Gong DZ, Zou Y, Li YS, Wu YH, Yuan B, Guan LL, Wu Q, Gao ZQ, Liu LJ. Effects of glucagon-like peptide-2 on the recovery of structure and function of small intestinal following orthotopic transplantation. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(18):3401-3405(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-18/18k-3401(ps).pdf]