Rubin D C, Swietlicki E A, Wang J L, Dodson B D, Levin M S
Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):G143-52. doi: 10.1152/ajpgi.1996.270.1.G143.
After massive small bowel resection, the remnant gut epithelium undergoes an adaptive response marked by an increase in villus height, crypt depth, and crypt cell production rate. Although morphological features of gut adaptation have been well characterized, the differentiation status and response of epithelial cells populating the adaptive villus is unclear. To address these issues, cell-specific and spatial patterns of expression of a set of enterocytic genes were characterized in rats after 70% small bowel resection. The liver and intestinal (I) fatty acid binding protein (FABP) and apolipoprotein A-I (apo A-I) and apo A-IV genes were studied because they exhibit unique regional and cell-specific patterns of expression in the developing and adult gut. At 48 h after surgery, apo A-IV and I-FABP mRNA levels were increased up to 3.5-fold in adaptive remnant ileum compared with sham-operated or sham-resected control ileum. In situ hybridization and immunohistochemical analyses revealed a marked increase in enterocytic apo A-IV mRNA and protein expression in the adaptive ileum, from villus base to tip but not in crypts. By 1 wk after resection, apo A-IV, but not I-FABP, mRNA levels remained elevated in remnant ileum, although duodenal I-FABP mRNA levels were still increased. In contrast, apo A-I mRNA levels were not significantly induced. These results indicate that the enterocyte can respond acutely to loss of small bowel surface area by increasing expression of several genes. This compensatory enterocytic response is spatially (from duodenum to ileum) and temporally regulated. These results suggest initiation of the adaptive response occurs by way of a complex set of molecular pathways involving villus and crypt cells.
在进行大规模小肠切除术后，残余肠道上皮会经历一种适应性反应，其特征为绒毛高度增加、隐窝深度增加以及隐窝细胞生成率提高。尽管肠道适应性的形态学特征已得到充分描述，但构成适应性绒毛的上皮细胞的分化状态及反应仍不清楚。为解决这些问题，对一组肠细胞基因在大鼠70%小肠切除术后的细胞特异性和空间表达模式进行了表征。研究了肝脏和肠道（I）脂肪酸结合蛋白（FABP）以及载脂蛋白A-I（apo A-I）和apo A-IV基因，因为它们在发育中和成年肠道中呈现出独特的区域和细胞特异性表达模式。术后48小时，与假手术或假切除对照回肠相比，适应性残余回肠中apo A-IV和I-FABP mRNA水平增加了高达3.5倍。原位杂交和免疫组织化学分析显示，适应性回肠中从绒毛基部到顶端的肠细胞apo A-IV mRNA和蛋白表达显著增加，但隐窝中未增加。切除术后1周，尽管十二指肠I-FABP mRNA水平仍升高，但残余回肠中apo A-IV mRNA水平仍然升高，而I-FABP mRNA水平不再升高。相比之下，apo A-I mRNA水平未被显著诱导。这些结果表明，肠细胞可通过增加几种基因的表达来对小肠表面积的丧失做出急性反应。这种代偿性肠细胞反应在空间上（从十二指肠到回肠）和时间上受到调节。这些结果表明，适应性反应的启动是通过涉及绒毛和隐窝细胞的一组复杂分子途径实现的。
