Mechanisms regulating nutrient induced motor patterns in the isolated small intestine

小肠的运动对食物的消化和吸收至关重要，在饭后3-4小时内，小肠的运动有两种基本模式。它们是混合（或分割）和推进（或蠕动）。虽然这是一个正在进行的研究课题，但人们对控制推进力的基本机制了解甚多，主要是因为这种行为很容易在肠道的孤立部分中看到，因此有可能进行高度控制的实验来识别系统的各种细胞成分。相比之下，混合只在完整的动物中被可靠地观察到，这使得研究这种行为的详细机制变得更加困难。我们所知道的是，一顿饭的成分控制着在小肠任何位置看到的混合和推进的相对数量。我们最近在离体小肠（十二指肠和/或空肠）中发现了一种收缩模式，这种收缩模式是由肠道中营养物质的存在引起的，与在完整动物中看到的混合行为非常相似。我们已经证明，这种模式取决于神经细胞的活动，包括那些刺激肠道肌肉的神经细胞，还取决于脂肪和其他营养物质从肠壁内壁释放的激素的活动。这项提议的目的是确定营养物质如何相互作用产生这种收缩模式，特定类型的神经细胞的相对作用以及营养物质释放的局部激素起作用的位置。这一点很重要，因为增加混合推进的比例可以增强膳食中营养物质的吸收，因此，如果启动混合行为的机制可以通过特定营养物质以可预测的方式调节，那么吸收可以在各种吸收不良综合征中得到加强。

The movements of the small intestine are essential for the digestion and absorption of a meal and consist of two basic patterns during a 3-4 hour period after a meal. These are mixing (or segmentation) and propulsion (or peristalsis). Although it is the subject of ongoing study, much is known about the basic mechanisms that control propulsion, largely because this behaviour is readily seen in isolated segments of gut so it is possible to undertake highly controlled experiments to identify the various cellular components of the system. By contrast, mixing has only been reliably seen in intact animals making studies of the detailed mechanisms responsible for this behaviour much more difficult. What is known is that the composition of a meal controls the relative amount of mixing and propulsion seen at any location along the small intestine. We have recently identified a pattern of contractions in isolated small intestine (duodenum and-or jejunum) that is induced by the presence of a nutrient in the intestine and appears very similar to the mixing behaviour seen in the intact animal. We have shown that this pattern depends on the activity of nerve cells including those that excite the gut muscle and that it depends on the activity of a hormone released from the lining of the gut wall by fats and other nutrients. The aims of this proposal are to identify how nutrients interact to produce this pattern of contractions, the relative roles of specific types of nerve cells and the sites at which the local hormones released by nutrients act. This is important because increasing the proportion of mixing to propulsion enhances the absorption of nutrient from a meal, so if the mechanisms that initiate mixing behaviour can be regulated in a predictable way by specific nutrient, absorption can be enhanced in various malabsorption syndromes.