Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation
Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation
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DOI：
10.3791/4086
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发表时间：
2012-09-01
影响因子：
1.2
通讯作者：
Wehner, Sven
中科院分区：
文献类型：
--
作者：
Vilz, Tim O.;Overhaus, Marcus;Wehner, Sven
胃肠道炎症是多种人类疾病的常见原因。动物研究模型在研究肠道病理的复杂细胞和分子方面至关重要。虽然图尼卡粘膜通常是许多炎性疾病的感兴趣器官，但最近的研究表明，肌层外（ME）也是一个高度免疫活性的器官，它含有密集的常驻免疫细胞网络。（1，2）这些工作是在标准化的肠操作（IM）模型中进行的，该模型导致肠壁炎症，主要限于ME。临床上，这种炎症导致长期的肠动力障碍，称为术后肠梗阻（POI），这是腹部手术后常见且不可避免的并发症。(3)炎症的特征是释放促炎介质如IL-6（4）或IL-1 β或抑制性神经递质如一氧化氮（NO）。(5)随后，大量的免疫细胞外渗到ME中，由多形核中性粒细胞（PMN）和单核细胞占主导地位，并最终维持POI。(2)这种肠麻痹持续数天，导致吸入、细菌移位和感染并发症的风险增加，直至败血症和多器官衰竭，并造成高经济负担。(6)In本文我们展示了IM的标准化模型和胃肠传输（GIT）和结肠传输的体内评估。此外，我们证明了一种方法，分离的ME从图尼卡粘膜免疫分析，这是至关重要的，以区分这两个高度免疫活性的肠壁室的炎症反应。所有的分析都很容易转移到任何其他研究模型，影响胃肠道功能。
Inflammation of the gastrointestinal tract is a common reason for a variety of human diseases. Animal research models are critical in investigating the complex cellular and molecular of intestinal pathology. Although the tunica mucosa is often the organ of interest in many inflammatory diseases, recent works demonstrated that the muscularis externa (ME) is also a highly immunocompetent organ that harbours a dense network of resident immunocytes. (1,2) These works were performed within the standardized model of intestinal manipulation (IM) that leads to inflammation of the bowel wall, mainly limited to the ME. Clinically this inflammation leads to prolonged intestinal dysmotility, known as postoperative ileus (POI) which is a frequent and unavoidable complication after abdominal surgery. (3) The inflammation is characterized by liberation of proinflammatory mediators such as IL-6(4) or IL-1 beta or inhibitory neurotransmitters like nitric oxide (NO). (5) Subsequently, tremendous numbers of immunocytes extravasate into the ME, dominated by polymorphonuclear neutrophils (PMN) and monocytes and finally maintain POI. (2) Lasting for days, this intestinal paralysis leads to an increased risk of aspiration, bacterial translocation and infectious complications up to sepsis and multi organ failure and causes a high economic burden. (6)In this manuscript we demonstrate the standardized model of IM and in vivo assessment of gastrointestinal transit (GIT) and colonic transit. Furthermore we demonstrate a method for separation of the ME from the tunica mucosa followed by immunological analysis, which is crucial to distinguish between the inflammatory responses in these both highly immunoactive bowel wall compartments. All analyses are easily transferable to any other research models, affecting gastrointestinal function.