Erben Ulrike, Loddenkemper Christoph, Doerfel Katja, Spieckermann Simone, Haller Dirk, Heimesaat Markus M, Zeitz Martin, Siegmund Britta, Kühl Anja A
Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany ; Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin Berlin, Germany.
Pathotres Joint Practice for Pathology Berlin, Germany.
Int J Clin Exp Pathol. 2014 Jul 15;7(8):4557-76. eCollection 2014.
Histomorphology remains a powerful routine evaluating intestinal inflammation in animal models. Emphasizing the focus of a given animal study, histopathology can overstate differences between established models. We aimed to systematize histopathological evaluation of intestinal inflammation in mouse models facilitating inter-study comparisons. Samples of all parts of the intestinal tract from well-established mouse models of intestinal inflammation were evaluated from hematoxylin/eosin-stained sections and specific observations confirmed by subsequent immunohistochemistry. Three main categories sufficiently reflected the severity of histopathology independent of the localization and the overall extent of an inflammation: (i) quality and dimension of inflammatory cell infiltrates, (ii) epithelial changes and (iii) overall mucosal architecture. Scoring schemata were defined along specified criteria for each of the three categories. The direction of the initial hit proved crucial for the comparability of histological changes. Chemical noxes, infection with intestinal parasites or other models where the barrier was disturbed from outside, the luminal side, showed high levels of similarity and distinct differences to changes in the intestinal balance resulting from inside events like altered cytokine responses or disruption of the immune cell homeostasis. With a high degree of generalisation and maximum scores from 4-8 suitable scoring schemata accounted specific histopathological hallmarks. Truly integrating demands and experiences of gastroenterologists, mouse researchers, microbiologists and pathologists we provide an easy-to-use guideline evaluating histomorphology in mouse models of intestinal inflammation. Standard criteria and definitions facilitate classification and rating of new relevant models, allow comparison in animal studies and transfer of functional findings to comparable histopathologies in human disease.
组织形态学仍然是评估动物模型肠道炎症的有力常规方法。强调特定动物研究的重点时，组织病理学可能会夸大既定模型之间的差异。我们旨在使小鼠模型肠道炎症的组织病理学评估系统化，以促进研究间的比较。从苏木精/伊红染色切片评估了成熟的肠道炎症小鼠模型肠道各部位的样本，并通过后续免疫组织化学确认了具体观察结果。三个主要类别足以反映组织病理学的严重程度，而与炎症的定位和总体范围无关：（i）炎性细胞浸润的质量和维度，（ii）上皮变化，以及（iii）整体黏膜结构。针对这三个类别中的每一个，根据特定标准定义了评分方案。最初损伤的方向被证明对组织学变化的可比性至关重要。化学毒物、肠道寄生虫感染或其他从外部（肠腔侧）干扰屏障的模型，与由内部事件（如细胞因子反应改变或免疫细胞稳态破坏）导致的肠道平衡变化显示出高度相似性和明显差异。具有高度普遍性且最高分为4 - 8分的合适评分方案考虑了特定的组织病理学特征。我们真正整合了胃肠病学家、小鼠研究人员、微生物学家和病理学家的需求与经验，提供了一份易于使用的指南，用于评估肠道炎症小鼠模型的组织形态学。标准标准和定义有助于对新的相关模型进行分类和评级，允许在动物研究中进行比较，并将功能研究结果转化为人类疾病中可比的组织病理学情况。
