Dekaney Christopher M, Fong Jerry J, Rigby Rachael J, Lund P Kay, Henning Susan J, Helmrath Michael A
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7223, USA.
Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1013-22. doi: 10.1152/ajpgi.00218.2007. Epub 2007 Sep 13.
Sustained increases in mucosal surface area occur in remaining bowel following massive intestinal loss. The mechanisms responsible for expanding and perpetuating this response are not presently understood. We hypothesized that an increase in the number of intestinal stem cells (ISC) occurs following intestinal resection and is an important component of the adaptive response in mice. This was assessed in the jejunum of mice 2-3 days, 4-5 days, 6-7 days, 2 wk, 6 wk, and 16 wk following ileocecal resection (ICR) or sham operation. Changes in ISC following ICR compared with sham resulted in increased crypt fission and were assayed by 1) putative ISC population (SP) by flow cytometry, 2) Musashi-1 immunohistochemistry, and 3) bromodeoxyuridine (BrdU) label retention. Observed early increases in crypt depth and villus height were not sustained 16 wk following operation. In contrast, long-term increases in intestinal caliber and overall number of crypts per circumference appear to account for the enhanced mucosal surface area following ICR. Flow cytometry demonstrated that significant increases in SP cells occur within 2-3 days following resection. By 7 days, ICR resulted in marked increases in crypt fission and Musashi-1 immunohistochemistry staining. Separate label-retention studies confirmed a 20-fold increase in BrdU incorporation 6 wk following ICR, confirming an overall increase in the number of ISC. These studies support that expansion of ISC occurs following ICR, leading to an overall increase number of crypts through a process of fission and intestinal dilation. Understanding the mechanism expanding ISCs may provide important insight into management of intestinal failure.
在大量肠道丢失后，剩余肠段的黏膜表面积会持续增加。目前尚不清楚导致这种反应扩大并持续存在的机制。我们假设，肠道切除术后肠道干细胞（ISC）数量会增加，并且这是小鼠适应性反应的重要组成部分。在回盲部切除（ICR）或假手术后2 - 3天、4 - 5天、6 - 7天、2周、6周和16周的小鼠空肠中对此进行了评估。与假手术相比，ICR后ISC的变化导致隐窝裂变增加，并通过以下方法进行测定：1）通过流式细胞术检测假定的ISC群体（SP）；2）进行Musashi - 1免疫组织化学检测；3）进行溴脱氧尿苷（BrdU）标记保留检测。观察到术后早期隐窝深度和绒毛高度增加，但在术后16周并未持续。相反，长期来看，肠道管径的增加以及每周长隐窝总数的增加似乎是ICR后黏膜表面积增加的原因。流式细胞术表明，切除术后2 - 3天内SP细胞显著增加。到第7天，ICR导致隐窝裂变和Musashi - 1免疫组织化学染色显著增加。单独的标记保留研究证实，ICR后6周BrdU掺入增加了20倍，证实了ISC数量的总体增加。这些研究支持ICR后ISC会发生扩增，通过裂变和肠道扩张过程导致隐窝总数总体增加。了解ISC扩增的机制可能为肠道衰竭的管理提供重要见解。
