School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan.
Am J Physiol Gastrointest Liver Physiol. 2022 Nov 1;323(5):G477-G487. doi: 10.1152/ajpgi.00175.2022. Epub 2022 Sep 20.
Gastrointestinal motility is crucial to gut health and has been associated with different disorders such as inflammatory bowel diseases and postoperative ileus. Despite rat and mouse being the two animal models most widely used in gastrointestinal research, minimal studies in rats have investigated gastrointestinal motility. Therefore, our study provides a comparison of colonic motility in the mouse and rat to clarify species differences and assess the relative effectiveness of each animal model for colonic motility research. We describe the protocol modifications and optimization undertaken to enable video imaging of colonic motility in the rat. Apart from the broad difference in terms of gastrointestinal diameter and length, we identified differences in the fundamental histology of the proximal colon such that the rat had larger villus height-to-width and villus height-to-crypt depth ratios compared with mouse. Since gut motility is tightly regulated by the enteric nervous system (ENS), we investigated how colonic contractile activity within each rodent species responds to modulation of the ENS inhibitory neuronal network. Here we used -nitro-l-arginine (l-NNA), an inhibitor of nitric oxide synthase (NOS) to assess proximal colon responses to the stimulatory effect of blocking the major inhibitory neurotransmitter, nitric oxide (NO). In rats, the frequency of proximal colonic contractions increased in the presence of l-NNA (vs. control levels) to a greater extent than in mice. This is despite a similar number of NOS-expressing neurons in the myenteric plexus across species. Given this increase in colonic contraction frequency, the rat represents another relevant animal model for investigating how gastrointestinal motility is regulated by the inhibitory neuronal network of the ENS. Mice and rats are widely used in gastrointestinal research but have fundamental differences that make them important as different models for different questions. We found that mice have a higher villi length-to-width and villi length-to-crypt depth ratio than rat in proximal colon. Using the ex vivo video imaging technique, we observed that rat colon has more prominent response to blockade of major inhibitory neurotransmitter (nitric oxide) in myenteric plexus than mouse colon.
胃肠道动力对于肠道健康至关重要，与炎症性肠病和术后肠梗阻等不同疾病有关。尽管大鼠和小鼠是胃肠道研究中最广泛使用的两种动物模型，但在大鼠中很少有研究探讨胃肠道动力。因此，我们的研究比较了小鼠和大鼠的结肠动力，以阐明物种差异，并评估每个动物模型在结肠动力研究中的相对有效性。我们描述了为使大鼠结肠动力的视频成像成为可能而进行的方案修改和优化。除了在胃肠道直径和长度方面存在广泛差异外，我们还发现近端结肠的基本组织学存在差异，与小鼠相比，大鼠的绒毛高度与宽度以及绒毛高度与隐窝深度的比值更大。由于肠道动力受肠神经系统 (ENS) 的紧密调节，我们研究了每种啮齿动物的结肠收缩活动如何对 ENS 抑制性神经元网络的调节做出反应。在这里，我们使用 -硝基-l-精氨酸（l-NNA），一种一氧化氮合酶 (NOS) 的抑制剂，来评估大鼠和小鼠近端结肠对主要抑制性神经递质一氧化氮 (NO) 阻断的刺激作用的反应。在大鼠中，与对照水平相比，在存在 l-NNA 的情况下，近端结肠收缩的频率增加到更大程度，而在小鼠中则不然。尽管在物种之间，肌间神经丛中的 NOS 表达神经元数量相似。鉴于结肠收缩频率的增加，大鼠代表了另一种用于研究胃肠道动力如何受 ENS 抑制性神经元网络调节的相关动物模型。小鼠和大鼠广泛用于胃肠道研究，但由于它们之间存在根本差异，因此它们作为不同问题的不同模型具有重要意义。我们发现，与大鼠相比，小鼠的近端结肠具有更高的绒毛长度与宽度以及绒毛长度与隐窝深度的比值。使用离体视频成像技术，我们观察到大鼠结肠对肌间神经丛中主要抑制性神经递质（一氧化氮）阻断的反应比小鼠结肠更为明显。
