CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division at the University of California Los Angeles, and VA Greater Los Angeles Health Care System, CA 90073, USA.
Peptides. 2010 Dec;31(12):2229-35. doi: 10.1016/j.peptides.2010.08.026. Epub 2010 Sep 15.
We investigated whether acute cold-induced vagal activation through brainstem thyrotropin-releasing hormone (TRH) signaling influences abdominal surgery-induced delayed gastric emptying (GE) in fasted rats. Laparotomy and cecal palpation or sham (short anesthesia alone) was performed 10 min before or 30 min after cold exposure (4-6°C) lasting 90 min. Non-nutrient GE was assessed during 70-90 min of cold exposure. Control groups remained at room temperature (RT). The stable TRH analog, RX-77368 (50 ng/rat) was injected intracisternally immediately before surgery and GE monitored 30-50 min postsurgery in rats maintained at RT. Plasma acyl (AG) and total ghrelin levels were assessed using the new RAPID blood processing method and radioimmunoassays. Desacyl ghrelin (DAG) was derived from total minus AG. In rats maintained at RT, abdominal surgery decreased GE by 60% compared to sham. Cold before or after surgery or RX-77368 normalized the delayed GE. In non-fasted rats, cold exposure increased plasma AG and DAG levels at 2 h (2.4- and 2.7-times, respectively) and 4 h (2.2- and 2.0-times, respectively) compared to values in rats maintained at RT. In fasted rats, abdominal surgery decreased AG and DAG levels by 2.4- and 2.1-times, respectively, at 90 min. Cold for 90 min after surgery normalized AG and DAG levels to those observed in sham-treated animals kept at RT. These data indicate that endogenous (cold exposure) and exogenous (TRH analog) activation of medullary TRH vagal signaling prevent abdominal surgery-induced delayed GE. The restoration of circulating AG levels inhibited by abdominal surgery may contribute to alleviate postoperative gastric ileus.
我们研究了通过脑垂体促甲状腺素释放激素 (TRH) 信号的急性冷诱导迷走神经激活是否会影响空腹大鼠腹部手术后胃排空延迟 (GE)。剖腹手术和盲肠触诊或假手术(仅短时间麻醉)在冷暴露 (4-6°C) 前 10 分钟或冷暴露后 30 分钟进行,持续 90 分钟。在冷暴露的 70-90 分钟期间评估非营养性 GE。对照组保持在室温 (RT)。在手术前立即将稳定的 TRH 类似物 RX-77368(50ng/大鼠)脑室内注射,并在 RT 下维持的大鼠手术后 30-50 分钟监测 GE。使用新的 RAPID 血液处理方法和放射免疫测定法评估血浆酰基 (AG) 和总 ghrelin 水平。从总减去 AG 得出去酰基 ghrelin (DAG)。在 RT 下维持的大鼠中,腹部手术后的 GE 减少了 60%,与假手术相比。手术前或手术后的冷暴露或 RX-77368 使延迟的 GE 正常化。在非禁食大鼠中,与 RT 下维持的大鼠相比,冷暴露在 2 小时(分别增加 2.4-和 2.7 倍)和 4 小时(分别增加 2.2-和 2.0 倍)时增加了血浆 AG 和 DAG 水平。在禁食大鼠中,腹部手术后 90 分钟时 AG 和 DAG 水平分别减少了 2.4-和 2.1 倍。手术后 90 分钟的冷暴露使 AG 和 DAG 水平正常化至 RT 下接受 sham 治疗的动物观察到的水平。这些数据表明,内源性(冷暴露)和外源性(TRH 类似物)激活髓质 TRH 迷走神经信号可防止腹部手术引起的延迟 GE。腹部手术后抑制的循环 AG 水平的恢复可能有助于缓解术后胃瘫。