Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs
Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs
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DOI：
10.1152/ajpgi.00280.2011
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发表时间：
2012-01-01
影响因子：
4.5
通讯作者：
Moore, David D.
中科院分区：
文献类型：
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作者：
Jain, Ajay Kumar;Stoll, Barbara;Moore, David D.
Jain AK，Stoll B，Burrin DG，Holst JJ，摩尔DD.肠内胆汁酸治疗改善新生猪肠外营养相关肝病和肠粘膜萎缩。美国生理学杂志胃肠和肝脏生理学302：G218-G224，2012年。首次发表于2011年11月17日; doi：10.1152/ajpgi.00280.2011。全肠外营养（TPN）对肠道功能受损的患者至关重要，但会导致肠外营养相关性肝病（PNALD）。TPN破坏胆汁酸的正常肠肝循环，我们假设它会降低新描述的代谢激素成纤维细胞生长因子-19（FGF 19）以及胰高血糖素样肽-1和-2（GLP-1和GLP-2）的肠道表达。我们通过用鹅去氧胆酸（CDCA）治疗新生仔猪PNALD模型来测试恢复胆汁酸的效果。新生猪接受肠内喂养（EN）、TPN或TPN + CDCA 14天，通过血清标志物、组织学和关键调节肽水平评估反应。与EN对照组相比，TPN组的胆汁淤积和脂肪变性表现为血清总胆红素和直接胆红素水平升高以及胆汁酸和肝脏甘油三酯（TG）含量升高。与TPN组相比，CDCA治疗使直接胆红素水平提高了近4倍，并使血清胆汁酸和肝脏TG正常化。与EN组相比，TPN组血浆中的FGF 19、GLP-1和GLP-2降低，但均由CDCA处理诱导。与EN组相比，TPN组以重量和绒毛/隐窝比为标志的肠粘膜生长显著减少，CDCA治疗增加了这两个参数。这些结果表明，TPN期间循环FGF 19的减少可能有助于PNALD。此外，我们表明，肠内CDCA不仅解决PNALD，但作为一个有效的肠道营养剂和促分泌素GLP-2。
Jain AK, Stoll B, Burrin DG, Holst JJ, Moore DD. Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs. Am J Physiol Gastrointest Liver Physiol 302: G218-G224, 2012. First published November 17, 2011; doi:10.1152/ajpgi.00280.2011.-Total parenteral nutrition (TPN) is essential for patients with impaired gut function but leads to parenteral nutrition-associated liver disease (PNALD). TPN disrupts the normal enterohepatic circulation of bile acids, and we hypothesized that it would decrease intestinal expression of the newly described metabolic hormone fibroblast growth factor-19 (FGF19) and also glucagon-like peptides-1 and -2 (GLP-1 and GLP-2). We tested the effects of restoring bile acids by treating a neonatal piglet PNALD model with chenodeoxycholic acid (CDCA). Neonatal pigs received enteral feeding (EN), TPN, or TPN + CDCA for 14 days, and responses were assessed by serum markers, histology, and levels of key regulatory peptides. Cholestasis and steatosis were demonstrated in the TPN group relative to EN controls by elevated levels of serum total and direct bilirubin and also bile acids and liver triglyceride (TG) content. CDCA treatment improved direct bilirubin levels by almost fourfold compared with the TPN group and also normalized serum bile acids and liver TG. FGF19, GLP-1, and GLP-2 were decreased in plasma of the TPN group compared with the EN group but were all induced by CDCA treatment. Intestinal mucosal growth marked by weight and villus/crypt ratio was significantly reduced in the TPN group compared with the EN group, and CDCA treatment increased both parameters. These results suggest that decreased circulating FGF19 during TPN may contribute to PNALD. Moreover, we show that enteral CDCA not only resolves PNALD but acts as a potent intestinal trophic agent and secretagogue for GLP-2.