van Bree Sjoerd Hw, Nemethova Andrea, van Bovenkamp Fleur S, Gomez-Pinilla Pedro, Elbers L, Di Giovangiulio Martina, Matteoli Gianluca, van Vliet Jan, Cailotto Cathy, Tanck Michael Wt, Boeckxstaens Guy Ee
Tytgat institute of Liver and Intestinal Research, Department of Gastroenterology & Hepatology, Academic Medical Center Amsterdam, the Netherlands.
Int J Physiol Pathophysiol Pharmacol. 2012;4(4):219-27. Epub 2012 Dec 26.
Postoperative ileus (POI) is characterized by a transient inhibition of coordinated motility of the gastrointestinal (GI) tract after abdominal surgery and leads to increased morbidity and prolonged hospitalization. Currently, intestinal manipulation of the intestine is widely used as a preclinical model of POI. The technique used to manipulate the intestine is however highly variable and difficult to standardize, leading to large variations and inconsistent findings between different investigators. Therefore, we developed a device by which a fixed and adjustable pressure can be applied during intestinal manipulation.
The standardized pressure manipulation method was developed using the purpose-designed device. First, the effect of graded manipulation was examined on postoperative GI transit. Next, this new technique was compared to the conventional manipulation technique used in previous studies. GI transit was measured by evaluating the intestinal distribution of orally gavaged fluorescein isothiocyanate (FITC)-labeled dextran. Infiltration of myeloperoxidase positive cells and cytokine production (ELISA) in the muscularis externa of the intestine were assessed.
Increasing pressures resulted in a graded reduction of intestinal transit and was associated with intestinal inflammation as demonstrated by influx of leukocytes and increased levels of IL-6, IL-1β and MCP-1 compared to control mice. With an applied pressure of 9 grams a similar delay in intestinal transit could be obtained with a smaller standard deviation, leading to a reduced intra-individual variation.
This method provides a reproducible model with small variation to study the pathophysiology of POI and to evaluate new anti-inflammatory strategies.
术后肠梗阻（POI）的特征是腹部手术后胃肠道（GI）协调运动的短暂抑制，并导致发病率增加和住院时间延长。目前，肠道操作被广泛用作POI的临床前模型。然而，用于操作肠道的技术高度可变且难以标准化，导致不同研究者之间的结果差异很大且不一致。因此，我们开发了一种装置，可在肠道操作过程中施加固定且可调节的压力。
使用专门设计的装置开发了标准化压力操作方法。首先，研究分级操作对术后胃肠道转运的影响。接下来，将这项新技术与先前研究中使用的传统操作技术进行比较。通过评估口服灌胃异硫氰酸荧光素（FITC）标记的葡聚糖在肠道中的分布来测量胃肠道转运。评估肠道肌层中髓过氧化物酶阳性细胞的浸润和细胞因子产生（ELISA）。
压力增加导致肠道转运分级降低，并与肠道炎症相关，与对照小鼠相比，白细胞流入以及IL-6、IL-1β和MCP-1水平升高证明了这一点。施加9克压力时，肠道转运延迟相似，但标准差更小，导致个体内差异减小。
该方法提供了一个变异小的可重复模型，用于研究POI的病理生理学和评估新的抗炎策略。
