Linderoth Ann, Prykhod'ko Olena, Pierzynowski Stefan G, Westrom Bjorn R
Department of Cell and Organism Biology, Animal Physiology, Lund University, Lund, Sweden.
Biol Neonate. 2006;89(1):60-8. doi: 10.1159/000088563. Epub 2005 Sep 26.
The lectin, phytohemagglutinin (PHA) has been shown to induce growth and functional maturation of the gastrointestinal (GI) tract in suckling rats.
To investigate the effect of the administration route, and whether enteral exposure to PHA was necessary to induce functional maturation.
Fourteen-day-old rats were daily administered PHA via orogastric feeding (0.05 mg PHA/g BW) or via subcutaneous injection (0.05 or 0.005 mg PHA/g BW) for 3 days, while the controls received saline orogastrically. At 17 days of age, organ weight, intestinal and pancreatic function, and plasma corticosterone levels were analyzed. Moreover, 14-days old pups receiving a single dose of PHA, enterally or parenterally, were sacrificed after 12 h and examined for organ PHA binding using immunohistochemistry.
Enteral PHA exposure resulted in PHA binding in the epithelial lining of the small intestine, increased gastrointestinal growth, reduced intestinal macromolecular absorption, altered the disaccharidase expression towards an adult-like pattern, and increased the pancreatic protein and trypsin contents. In contrast, parenteral PHA exposure (high dose) resulted in PHA-binding in extra-intestinal organs, increased liver and spleen weight, and decreased thymus weight. Moreover, the intestinal maltase activity increased moderately, and the transfer of BSA to blood plasma was partially reduced. Both PHA treatments led to elevated plasma corticosterone levels.
These results demonstrated that enteral exposure to PHA was necessary to induce the precocious maturation of the GI tract and the pancreas, while parenteral administration affects the extra-intestinal organs. Furthermore, the enteral effects were probably not mediated via a corticosteroid dependent pathway.
凝集素——植物血凝素(PHA)已被证明可诱导乳鼠胃肠道(GI)的生长和功能成熟。
研究给药途径的影响,以及肠道接触PHA是否是诱导功能成熟所必需的。
14日龄大鼠每天通过灌胃(0.05 mg PHA/g体重)或皮下注射(0.05或0.005 mg PHA/g体重)给予PHA,持续3天,而对照组经口给予生理盐水。在17日龄时,分析器官重量、肠道和胰腺功能以及血浆皮质酮水平。此外,14日龄幼崽经肠内或肠外给予单剂量PHA,12小时后处死,用免疫组织化学法检测器官PHA结合情况。
肠道接触PHA导致小肠上皮内衬有PHA结合,胃肠道生长增加,肠道大分子吸收减少,双糖酶表达改变为类似成年的模式,并增加胰腺蛋白和胰蛋白酶含量。相比之下,肠外接触PHA(高剂量)导致肠外器官有PHA结合,肝脏和脾脏重量增加,胸腺重量减轻。此外,肠道麦芽糖酶活性适度增加,牛血清白蛋白向血浆的转运部分减少。两种PHA处理均导致血浆皮质酮水平升高。
这些结果表明,肠道接触PHA是诱导胃肠道和胰腺早熟成熟所必需的,而肠外给药会影响肠外器官。此外,肠道效应可能不是通过皮质类固醇依赖途径介导的。