Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome
Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome
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DOI：
10.1007/s10620-018-5420-x
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发表时间：
2019-05-01
影响因子：
3.1
通讯作者：
Witte, Maria
中科院分区：
文献类型：
--
作者：
Berlin, Peggy;Reiner, Johannes;Witte, Maria
背景短肠综合征是由广泛的小肠切除引起的，并诱导剩余肠道的适应性。回盲肠切除(ICR)是人类最常见的情况。绒毛肥大是黏膜适应的标志之一，但粘膜适应的作用机制尚不完全清楚。目的本研究的目的是建立一种临床相关的短肠综合征小鼠模型，并确定其结果预测因素和适应机制。以小肠横断术为对照。所有小鼠都进行了尸检。记录小鼠的存活率、体重、健康评分、大便水分含量、血浆醛固酮浓度和细胞旁通透性。结果与对照组一样，切除小鼠出现明显的腹泻，大便水分增加。随之而来的是随之而来的持续减肥。绒毛长度增加，但不与适应呈正相关。第14天血浆醛固酮浓度与体重呈负相关。ICR后，肠上皮(即紧密连接)钠通透性增加。结论40%ICR可导致中至重度短肠综合征。对短肠情况的成功适应涉及到绒毛的伸长，但仅与绒毛伸长的程度无关。此外，肠上皮钠通透性的增加促进了钠偶联溶质的运输。醛固酮增多症与体重下降的严重程度相关，表明体积消耗，并抵消水分丢失。
BackgroundShort bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood.AimsThe aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation.MethodsMale C57BL6/J mice underwent 40% ICR and were followed for 7 or 14days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded.ResultsUnlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased.Conclusions40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss.