How spinal afferent nerves cause vasodilation of mesenteric arteries

胃肠道的健康功能需要在不同需求时期有充足的血液供应。肠道血液供应不足会导致从轻微到致命的各种严重疾病。肠道供血减少是引发多器官衰竭综合征的诱因；是大手术、创伤或出血后危重病人死亡的主要原因。据信，在血流减少的时期，肠道内层的损伤会引发全身的炎症机制。肠系膜缺血是一种以慢性、非闭塞性形式发生的疾病，或以急性发作的形式发生，通常是致命的。众所周知，血液供应的暂时增加在保护肠道免受酸、毒素和病原体攻击方面也起到了至关重要的作用。血液供应增加的主要机制是动脉血管扩张。这通过局部机制在损伤部位局部发生，但上游动脉更广泛地扩张，由直接支配血管的感觉神经元分支介导。目前，还没有关于这些感觉神经元是如何激活的信息。这对于理解它们是如何工作的至关重要。我们假设这些感觉神经元是由肠壁中的化学和机械刺激激活的，这使它们向上游的动脉释放血管扩张化学物质，从而放大局部血流量的增加。我们将通过记录感觉神经来测试这一点，识别投射到血管的感觉神经，并确定它们对哪些化学物质和机械刺激感到兴奋。然后，我们将使用我们最近开发的一种方法，将它们填充到染料中，以可视化它们在肠壁内外的分支模式。通过这种方式，我们将了解这种强大的保护机制是如何在需要的时候被激活的，以及在某些情况下它可能会如何失效。

Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger inflammatory mechanisms throughout the body. Mesenteric ischaemia is a disorder which occurs as a chronic, non-occlusive form, or as acute episodes, which are often lethal, . Temporary increases in blood supply are also known to play a vital role in protecting the gut from acid, toxins and attack by pathogens. The major mechanism underlying increases in bloody supply is dilation of arterial vessels. This occurs focally, at the site of damage, via local mechanisms, but this is supplemented by a more widespread dilation of arteries upstream, mediated by branches of sensory neurones that innervate blood vessels directly. Currently, there is no information about how these sensory neurones are activated. This is crucial to understand how they work. We hypothesise that these sensory neurones are activated by chemical and mechanical stimuli in the gut wall, which make them release vasodilator chemicals onto the arteries upstream and thus amplify the local increases in blood flow. We will test this by recording from sensory nerves, identifying the ones which project to blood vessels and determine which chemicals and mechanical stimuli they are excited by. We will then fill them with dye, using a method that we have recently developed, to visualise their branching patterns both inside and outside the gut wall. In this way, we will understand how this powerful protective mechanism is activated at times of need, and how it may fail under some circumstances.