Greig Chasen J, Cowles Robert A
Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
Microsc Res Tech. 2017 Jul;80(7):793-798. doi: 10.1002/jemt.22866. Epub 2017 Mar 13.
Quantification of intestinal mucosal growth typically relies on morphometric parameters, commonly villus height, as a surrogate for presumed changes in mucosal surface area (MSA). We hypothesized that using mathematical modeling based on multiple unique measurements would improve discrimination of the effects of interventions on MSA compared to standard measures. To determine the ability of mathematical modeling to resolve differences in MSA, a mouse model with enhanced serotonin (5HT) signaling known to stimulate mucosal growth was used. 5-HT signaling is potentiated by targeting the serotonin reuptake transporter (SERT) molecule. Selective serotonin reuptake inhibitor-treated wild-type (WT-SSRI), SERT-knockout (SERTKO), and wild-type C57Bl/6 (WT) mice were used. Distal ileal sections were H&E-stained. Villus height (VH), width (VW), crypt width (CW), and bowel diameter were used to calculate surface area enlargement factor (SEF) and MSA. VH alone for SERTKO and SSRI was significantly increased compared to WT, without a difference between SERTKO and WT-SSRI. VW and CW were significantly decreased for both SERTKO and WT-SSRI compared to WT, and VW for WT-SSRI was also decreased compared to SERTKO. These changes increased SEF and MSA for SERTKO and WT-SSRI compared to WT. Additionally, SEF and MSA were significantly increased for WT-SSRI compared to SERTKO. Mathematical modeling provides a valuable tool for differentiating changes in intestinal MSA. This more comprehensive assessment of surface area does not appear to correlate linearly with standard morphometric measures and represents a more comprehensive method for discriminating between therapies aimed at increasing functional intestinal mucosa.
肠道黏膜生长的量化通常依赖于形态测量参数，通常是绒毛高度，作为黏膜表面积（MSA）假定变化的替代指标。我们假设，与标准测量方法相比，基于多种独特测量的数学建模将提高对干预措施对MSA影响的辨别能力。为了确定数学建模解决MSA差异的能力，使用了一种已知能刺激黏膜生长的血清素（5HT）信号增强的小鼠模型。通过靶向血清素再摄取转运体（SERT）分子来增强5-HT信号。使用了经选择性血清素再摄取抑制剂处理的野生型（WT-SSRI）、SERT基因敲除（SERTKO）和野生型C57Bl/6（WT）小鼠。对回肠远端切片进行苏木精-伊红染色。使用绒毛高度（VH）、宽度（VW）、隐窝宽度（CW）和肠直径来计算表面积扩大因子（SEF）和MSA。与WT相比，SERTKO和SSRI单独的VH显著增加，SERTKO和WT-SSRI之间没有差异。与WT相比，SERTKO和WT-SSRI的VW和CW均显著降低，与SERTKO相比，WT-SSRI的VW也降低。与WT相比，这些变化增加了SERTKO和WT-SSRI的SEF和MSA。此外，与SERTKO相比，WT-SSRI的SEF和MSA显著增加。数学建模为区分肠道MSA的变化提供了一个有价值的工具。这种对表面积更全面的评估似乎与标准形态测量指标不存在线性相关，并且代表了一种更全面的方法，用于区分旨在增加功能性肠黏膜的治疗方法。
