Dept. of Nutritional Sciences, Univ. of Wisconsin, Madison, 53706, USA.
Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G338-47. doi: 10.1152/ajpgi.00165.2010. Epub 2010 Jun 10.
We previously reported that rats receiving total parenteral nutrition (TPN) undergo significant pancreatic atrophy characterized by reduced total protein and digestive enzyme expression due to a lack of intestinal stimulation by nutrients (Baumler MD, Nelson DW, Ney DM, Groblewski GE. Am J Physiol Gastrointest Liver Physiol 292: G857-G866, 2007). Essentially identical results were recently reported in mice fed protein-free diets (Crozier SJ, D'Alecy LG, Ernst SA, Ginsburg LE, Williams JA. Gastroenterology 137: 1093-1101, 2009), provoking the question of whether reductions in pancreatic protein and digestive enzyme expression could be prevented by providing amino acids orally or by intravenous (IV) infusion while maintaining intestinal stimulation with fat and carbohydrate. Controlled studies were conducted in rats with IV catheters including orally fed/saline infusion or TPN-fed control rats compared with rats fed a protein-free diet, oral amino acid, or IV amino acid feeding, all with oral carbohydrate and fat. Interestingly, neither oral nor IV amino acids were sufficient to prevent the pancreatic atrophy seen for TPN controls or protein-free diets. Oral and IV amino acids partially attenuated the 75-90% reductions in pancreatic amylase and trypsinogen expression; however, values remained 50% lower than orally fed control rats. Lipase expression was more modestly reduced by a lack of dietary protein but did respond to IV amino acids. In comparison, chymotrypsinogen expression was induced nearly twofold in TPN animals but was not altered in other experimental groups compared with oral control animals. In contrast to pancreas, protein-free diets had no detectable effects on jejunal mucosal villus height, total mass, protein, DNA, or sucrase activity. These data underscore that, in the rat, intact dietary protein is essential in maintaining pancreatic growth and digestive enzyme adaptation but has surprisingly little effect on small intestinal mucosa.
我们之前曾报道过，接受全肠外营养（TPN）的大鼠会出现明显的胰腺萎缩，其特征是由于缺乏营养物质对肠道的刺激，导致总蛋白和消化酶表达减少（Baumler MD、Nelson DW、Ney DM、Groblewski GE。Am J Physiol Gastrointest Liver Physiol 292：G857-G866，2007）。最近在接受无蛋白饮食的小鼠中也得到了基本相同的结果（Crozier SJ、D'Alecy LG、Ernst SA、Ginsburg LE、Williams JA。Gastroenterology 137：1093-1101，2009），这引发了一个问题，即通过口服或静脉输注提供氨基酸，同时用脂肪和碳水化合物维持肠道刺激，是否可以防止胰腺蛋白和消化酶表达减少。我们在带有静脉内（IV）导管的大鼠中进行了对照研究，包括口服喂养/盐水输注或 TPN 喂养对照组大鼠与接受无蛋白饮食、口服氨基酸或 IV 氨基酸喂养的大鼠进行比较，所有大鼠均口服碳水化合物和脂肪。有趣的是，口服和 IV 氨基酸都不足以预防 TPN 对照组或无蛋白饮食大鼠所见到的胰腺萎缩。口服和 IV 氨基酸部分减轻了胰腺淀粉酶和胰蛋白酶原表达减少 75-90%；然而，其值仍比口服喂养的对照组大鼠低 50%。脂肪酶表达因缺乏膳食蛋白而适度减少，但对 IV 氨基酸有反应。相比之下，在 TPN 动物中，糜蛋白酶原的表达几乎增加了两倍，但在其他实验组中与口服对照组动物相比没有变化。与胰腺不同，无蛋白饮食对空肠黏膜绒毛高度、总质量、蛋白质、DNA 或蔗糖酶活性没有可检测到的影响。这些数据强调，在大鼠中，完整的膳食蛋白对于维持胰腺生长和消化酶适应性是必不可少的，但对小肠黏膜的影响却出人意料地小。
