Neurogastroenterology Group, Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, UK.
Br J Pharmacol. 2013 Jan;168(1):28-43. doi: 10.1111/j.1476-5381.2012.02198.x.
Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance.
转化科学越来越强调在天然人体组织中测量功能。然而，这些研究必须面对患者年龄、性别、遗传背景和疾病的差异。本文将参考人类胃肠道（GI）的神经肌肉和神经分泌功能来讨论这些差异。在获得知情同意后，与外科医生（手术技术有助于最大限度地减少变量）和病理学家合作获取组织。由于直接从人类肌间神经元（嵌入在肌肉层之间）进行记录存在困难，因此通过测量内在神经电刺激引起的肌肉收缩/松弛来研究肠运动神经功能；反应具有区域性依赖性，通常涉及胆碱能和硝能表型。通过诱发涉及肠感觉和运动神经的蠕动反射，可以研究肠感觉功能，但这很少实现。由于黏膜下神经元更容易接近（在去除黏膜后），因此可以进行直接神经元记录。通过测量跨黏膜的短路电流变化来研究神经分泌功能。对于所有实验，都必须解决基本问题。由于组织来自患者，那么对照和疾病的影响是什么？功能需要多长时间才能完全恢复？年龄和性别相关差异的影响是什么？最佳样本量是多少？解决这些问题和其他问题可以最大限度地减少变异性，并提高人体组织研究的科学可信度。此类研究还减少了动物的使用。此外，动物和人类 GI 功能之间的许多差异也意味着，人类组织研究必须质疑使用未经证实的具有转化意义的动物品系的伦理有效性。
