Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus
Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus
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DOI：
10.1124/jpet.108.149211
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发表时间：
2009-06-01
影响因子：
3.5
通讯作者：
Greenwood-Van Meerveld, Beverley
中科院分区：
文献类型：
--
作者：
Venkova, Kalina;Mann, William;Greenwood-Van Meerveld, Beverley
胃饥饿素和胃饥饿素模拟物刺激食欲，增强胃动力。本研究探讨了ipamorelin（一种选择性生长激素促分泌剂和胃饥饿素受体激动剂）是否会加速胃肠道转运并改善术后肠梗阻（POI）啮齿动物模型的症状。禁食的雄性大鼠进行开腹和肠操作。在手术结束时，在近端结肠注入染料标记物以评估术后结肠运输时间，即第一次排便的时间。此外，定期监测粪便颗粒排出量、食物摄入量和体重48小时。在单次给药或2天重复给药方案（每天4次，间隔3小时）后，通过静脉滴注Ipamorelin （0.01-1 mg/kg）、生长激素释放肽(GHRP)-6 （20 mu g/kg）或载体（生理盐水）。与对照组相比，单剂量的异莫瑞林（1 mg/kg）或GHRP-6 （20 mu g/kg）可缩短患者第一次排便的时间，但对术后48小时的累积排便量、食物摄入量或体重增加没有影响。相反，反复给药（0.1或1mg /kg）可显著增加粪便颗粒排泄量、食物摄入量和体重增加。提示术后静脉输注伊莫瑞林可改善POI患者的症状。
Ghrelin and ghrelin mimetics stimulate appetite and enhance gastric motility. The present study investigates whether ipamorelin, a selective growth hormone secretagogue and agonist of the ghrelin receptor, would accelerate gastrointestinal transit and ameliorate the symptoms in a rodent model of postoperative ileus (POI). Fasted male rats were subjected to laparotomy and intestinal manipulation. At the end of surgery, a dye marker was infused in the proximal colon to evaluate postsurgical colonic transit time, which was the time to the first bowel movement. In addition, fecal pellet output, food intake, and body weight were monitored regularly for 48 h. Ipamorelin (0.01-1 mg/kg), growth hormone-releasing peptide (GHRP)-6 (20 mu g/kg), or vehicle (saline) were administered via intravenous bolus infusion after a single dosing or a 2-day repetitive dosing regimen (four doses a day at 3-h intervals). Compared with the vehicle, a single dose of ipamorelin (1 mg/kg) or GHRP-6 (20 mu g/kg) decreased the time to the first bowel movement but had no effect on cumulative fecal output, food intake, or body weight gain measured 48 h after the surgery. In contrast, repetitive dosing of ipamorelin (0.1 or 1 mg/kg) significantly increased the cumulative fecal pellet output, food intake, and body weight gain. The results suggest that postsurgical intravenous infusions of ipamorelin may ameliorate the symptoms in patients with POI.