Billeschou Anna, Hunt Jenna Elizabeth, Ghimire Aruna, Holst Jens J, Kissow Hannelouise
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
Biomedicines. 2021 Jan 7;9(1):46. doi: 10.3390/biomedicines9010046.
Intestinal adaptation is an important response and a natural repair mechanism in acute intestinal injury and is critical for recovery. Glucagon-like peptide 2 (GLP-2) has been demonstrated to enhance mucosal repair following intestinal damage. In this study, we aimed to investigate the role of GLP-2 receptor activation on intestinal protection and adaptation upon chemotherapy-induced intestinal injury. The injury was induced with a single injection of 5-fluorouracil in female GLP-2 receptor knockout (GLP-2R(-/-)) mice and their wild type (WT) littermates. The mice were euthanized in the acute or the recovery phase of the injury; the small intestines were analysed for weight changes, morphology, histology, inflammation, apoptosis and proliferation. In the acute phase, only inflammation was slightly increased in the GLP-2R(-/-) mice compared to WT. In the recovery phase, we observed the natural compensatory response with an increase in small intestinal weight, crypt depth and villus height in WT mice, and this was absent in the GLP-2R(-/-) mice. Both genotypes responded with hyperproliferation. From this, we concluded that GLP-2R signalling does not have a major impact on acute intestinal injury but is pivotal for the adaptive response in the small intestine.
肠道适应性是急性肠道损伤中的一种重要反应和自然修复机制，对恢复至关重要。胰高血糖素样肽2（GLP-2）已被证明可增强肠道损伤后的黏膜修复。在本研究中，我们旨在探讨激活GLP-2受体对化疗诱导的肠道损伤时肠道保护和适应性的作用。通过单次注射5-氟尿嘧啶诱导雌性GLP-2受体敲除（GLP-2R(-/-)）小鼠及其野生型（WT）同窝小鼠产生损伤。在损伤的急性期或恢复期对小鼠实施安乐死；分析小肠的重量变化、形态、组织学、炎症、凋亡和增殖情况。在急性期，与WT小鼠相比，GLP-2R(-/-)小鼠仅炎症略有增加。在恢复期，我们观察到WT小鼠出现小肠重量增加、隐窝深度和绒毛高度增加的自然代偿反应，而GLP-2R(-/-)小鼠则无此反应。两种基因型均出现增殖过度。由此我们得出结论，GLP-2R信号传导对急性肠道损伤没有重大影响，但对小肠的适应性反应至关重要。
