【作者】 伍远航； 朱亮； 宫德正； 邹原； 吴云红； 王亚辰； 汪冰； 温静； 苏剑瑶； 尚健； 关莉莉； 吴琼； 袁博； 王立明； 罗福文； 贾玉洁；

【Author】 Wu yuanhang1,Zhu liang2 (Corresponding author),Gong dezheng2,Zou yuan2,Wu yun hong3,Wang yachen1,Wang bing1,Wen jing1,Shu jianyao1,Shang jian1,Guan lili2,Wu qiong2,Yuan bo2,Wang liming4,Luo fuwen4,Jiang yujie5 1. Colleges of Basic Medical Sciences,Dalian Medical University,Dalian 116044,China. 2. Department of Physiology,Dalian Medical University,Dalian 116044,China. 3. College of Health Administration,Dalian Medical University,Dalian,116044,china. 4. Division of Organ Transplantation,Dalian Medical University,Dalian,116027,China. 5. Pathology of Physiology,Dalian Medical University,Dalian 116044,China.

【机构】 大连医科大学基础医学院； 大连医科大学生理教研室； 大连医科大学社会科学和管理科学学院； 大连医科大学器官移植中心； 大连医科大学病理生理教研室；

【摘要】 背景:小肠移植是治疗不可逆肠衰竭的根本有效办法,但是排斥、感染、保存、再灌注损伤、移植肠去神经、淋巴回流障碍引起的移植肠损伤妨碍了小肠移植的效果。随着排斥免疫和抗排斥药物研究的深入,目前移植排斥方面已取得了较大进步。功能恢复是小肠移植的重点研究方向,采取有效手段促进术后移植肠结构和功能的恢复,对于减少术后并发症,提高小肠移植成功率有着十分重要的意义。胰高血糖素样肽-2(glucagon-likepeptide-2,GLP-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,GLP-2的作用具有肠道特异性,且促生长作用更强。GLP-2对非移植肠的保护作用已得到广泛证实。目的:探讨胰高血糖素样肽-2(GLP-2)对大鼠原位移植小肠上皮的增殖和超微结构的修复的影响。方法:75只Wistar大鼠按随机数字表法分为3组,小肠移植组(n=30),胰高血糖素样肽-2组(n=30),假手术组(n=15)。小肠移植采用改良的kort法行二步法大鼠原位小肠移植。胰高血糖素样肽-2组小肠移植后经GLP-2处理,250μg/kg,2次/d皮下注射,连续给3d。假手术组和小肠移植组分别给相应体积的0.01mol/LPBS。术后2周行肠粘膜组织病理学HE染色,透射电镜检查。术后2周行肠粘膜组织病理学检查,并分别于2周、4周、8周检测血浆白蛋白水平,移植肠功能酶(Na+,K+-ATP酶、双糖酶)活性,移植小肠对木糖的吸收。结果:组织学观察术后2周GLP-2组肠粘膜绒毛高度,隐窝深度显著高于移植组。电镜观察GLP-2组微绒毛整齐,单位横断面上的微绒毛数目较多,且较长,上皮细胞间紧密连接、线粒体和细胞核形态正常,小肠移植组微绒毛排列紊乱、高度明显低于GLP-2组,上皮细胞间紧密连接增宽、部分线粒体程空泡状变性、部分细胞核染色质边集呈凋亡征象。原位移植组,木糖的吸收在2周时显著低于假手术组,4周时无显著性差异,小肠功能酶活性在2周下降明显,4周时双糖酶的功能恢复正常,8周时Na+-K+ATP酶也接近正常;GLP-2组,木糖吸收和双糖酶的活性在2周时恢复正常,4周时Na+-K+ATP酶恢复正常。结论:外源性GLP-2促进大鼠原位移植小肠吸收功能和超微结构的恢复。更多还原

【Abstract】 Background Intestinal transplantation (IT) may eventually become the definitive therapeutic modality for irreversible intestinal failure. However, the small intestinal graft injury limits the success and widespread use of IT. Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that exhibits striking intestinotropic properties. For the first time, we explored the influence of glucagon-like peptide-2(GLP-2) on the recovery of ultrastructure and function of orthotopic intestinal transplantation (OIT) in rats. Objective:To explore the influence of glucagon-like peptide-2(GLP-2) recovery of graft mucosal cell proliferation and ultrastructure after orthotopic intestinal transplantation in the rat. Methods:Seventy-five Wistar rats were randomly divided into 3 groups:sham group (Con, n =15), simple orthotopic intestine transplantation group (OIT, n =30), orthotopic intestine transplantation with GLP-2 treatment group (GLP-2, n =30). Two-step orthotopic intestinal transplantation (OIT) using Kort’s method modified by us. Rats receive subcutaneous injection of either GLP-2 (GLP-2 group; 250μg/kg/day), phosphate-buffered saline (Con group and OIT group). The histological changes stained with HE and changes of Microvilli by electron microscopy in the intestinal mucosal tissue were observed at 2 weeks after operation. Separate experiments were performed 2,4and 8 weeks after surgery to measure plasma albumin level, absorbability of D-xylose with the colorimetry in small intestine, functional enzyme activity (disaccharides, Na+/K+-ATPase) in rat small intestinal epithelium. Results:Compared with OIT group, the intestinal villous height and crypt depth in GLP-2 group were increased significantly. Electron microscopy demonstrated that GLP-2 treatment increased number and length of Microvilli of the epithelial cells. In OIT group, activity of disaccharides and serum D-xylose level returned to baseline at 4 weeks and mucosal Na+/K+-ATPase activity return to baseline at 8 weeks. In GLP-2 group, activity of disaccharides and serum D-xylose level returned to baseline at 2 weeks and mucosal Na+/K+-ATPase activity return to baseline at 4 weeks. Conclusion:Glucagon-like peptide-2 supplementation can promote recovery of absorption function and ultrastructure of orthotopic small intestinal transplantation in rats.更多还原