Effect of the ghrelin receptor agonist TZP-101 on colonic transit in a rat model of postoperative ileus
Effect of the ghrelin receptor agonist TZP-101 on colonic transit in a rat model of postoperative ileus
复制标题
DOI：
10.1016/j.ejphar.2008.12.011
复制
发表时间：
2009-02-14
影响因子：
5
通讯作者：
Greenwood-Van Meerveld, Beverley
中科院分区：
文献类型：
--
作者：
Fraser, Graeme L.;Venkova, Kalina;Greenwood-Van Meerveld, Beverley
生长激素促分泌素受体（生长激素释放肽受体）的天然配体生长激素释放肽是在上胃肠道中具有促动力作用的促食欲肠激素。先前，我们已经在术后肠梗阻的啮齿动物模型中显示合成的生长激素释放肽受体激动剂TZP-101防止胃排空延迟并改善小肠传输。本研究的目的是研究TZP-101是否影响术后肠梗阻大鼠的结肠运输和食物摄入。禁食大鼠用吗啡处理，并在异氟烷麻醉下进行剖腹手术。手术后，将动物置于干净的饲养笼中，监测粪粒排出量和摄食量48小时。在手术后0小时、2小时和4小时以3次静脉推注施用TZP-101或媒介物。与媒介物相比，TZP-101（0.03-lmg/kg）剂量依赖性地减少至第一次排便的时间并且增加在手术后12小时和24小时测量的粪粒输出。TZP-101的给药与食物摄入的显著改变无关。总之，这项研究提供了第一个实验证据，表明一种新型的胃饥饿素受体激动剂可以改善术后肠梗阻大鼠的大肠功能，这表明TZP-101在临床上可能有助于加速上消化道转运，缩短术后首次排便的时间。由爱思唯尔公司出版
Ghrelin, the natural ligand of the growth hormone secretagogue receptor (ghrelin receptor), is an orexigenic gut hormone with prokinetic action in the upper gastrointestinal tract Previously we have shown in a rodent model of postoperative ileus that the synthetic ghrelin receptor agonist TZP-101 prevents the delay in gastric emptying and improves small intestinal transit. The goal of the present study was to investigate whether TZP-101 affects colonic transit and food intake in rats with postoperative ileus. Fasted rats were treated with morphine and subjected to laparotomy under isoflurane anesthesia. Following surgery the animals were placed in clean home cages and fecal pellet output and food intake were monitored for 48 h. TZP-101 or vehicle were administered as 3 i.v. bolus infusions at 0 h, 2 h and 4 h post-surgery. TZP-101 (0.03-1 mg/kg) dose-dependently decreased the time to first bowel movement and increased fecal pellet output measured at 12 h and 24 h post-surgery compared to the vehicle. The administration of TZP-101 was not associated with a significant alteration in food intake. In conclusion, this study provides the first experimental evidence that a novel ghrelin receptor agonist improves large bowel function in rats with postoperative ileus, suggesting that TZP-101 may be useful in the clinic to accelerate upper gastrointestinal transit and to shorten the time to the first bowel movement following surgery. Published by Elsevier B.V.