Bueter Marco, Abegg Kathrin, Seyfried Florian, Lutz Thomas A, le Roux Carel W
Department of Surgery, University Hospital Zürich.
J Vis Exp. 2012 Jun 11(64):e3940. doi: 10.3791/3940.
Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation, increased energy expenditure, altered preference for food high in fat and sugar, altered salt and water handling of the kidney as well as alterations in gut microbiota. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating. During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%. Furthermore, surgery has been carried out almost exclusively in male rats of different strains and ages. Pre- and postoperative diets also varied significantly. Technical and experimental variations in published gastric bypass rat models complicate the comparison and identification of potential physiological mechanisms involved in gastric bypass. There is no clear evidence that any of these models is superior, but there is an emerging need for standardization of the procedure to achieve consistent and comparable data. This article therefore aims to summarize and discuss technical and experimental details of our previously validated and published gastric bypass rat model.
目前，治疗病态肥胖以实现显著且持续的体重减轻并已证实具有死亡率益处的最有效疗法是减肥手术。因此，近年来全球范围内减肥手术的数量稳步上升，其中 Roux-en-Y 胃旁路术（胃旁路手术）是最常实施的手术。在此背景下，了解胃旁路手术诱导并维持体重减轻的生理机制非常重要。这些机制尚未完全明确，但可能包括饥饿感降低和饱腹感增加、能量消耗增加、对高脂肪和高糖食物的偏好改变、肾脏对盐和水的处理改变以及肠道微生物群的改变。胃旁路手术后出现的这些变化可能至少部分源于手术对激素环境的改变，因为胃旁路手术会增加餐后肽 YY（PYY）和胰高血糖素样肽 1（GLP-1）的释放，这两种激素在有营养物质存在时由肠道释放，可减少进食。在过去二十年中，已经进行了大量使用大鼠的研究来进一步探究胃旁路手术后的生理变化。胃旁路大鼠模型已被证明是一种有价值的实验工具，这不仅是因为它能紧密模拟人类体重减轻的时间进程和幅度，还因为它能让研究人员控制和操纵关键的解剖学和生理学因素，包括使用适当的对照。因此，在其他地方更详细综述的文献中有大量可用的大鼠胃旁路模型。这些模型的确切手术技术描述差异很大，例如在胃囊大小、肠袢长度以及迷走神经的保留方面存在差异。如果有报告，死亡率似乎在 0%至 35%之间。此外，手术几乎完全在不同品系和年龄的雄性大鼠身上进行。术前和术后饮食也有很大差异。已发表的胃旁路大鼠模型中的技术和实验差异使得比较和确定胃旁路手术涉及的潜在生理机制变得复杂。没有明确证据表明这些模型中的任何一个更优越，但越来越需要对该手术进行标准化以获得一致且可比的数据。因此，本文旨在总结和讨论我们之前验证并发表的胃旁路大鼠模型的技术和实验细节。
