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美国圣路易斯大学医学院 儿科学系、儿童医学中心 生物化学与分子生物学系 内科医学系 背景：使用肠外营养（PN）进行营养支持与肠道萎缩相关。先前的研究表明肠内的鹅脱氧胆酸，一种法尼酯X受体（FXR）和胆汁酸受体TGR5的双效激动剂，可以改善这种情况。我们推测TGR5的激活可以引起肠道的生长，TGR5特异性激动剂齐墩果酸（OA）可以预防PN过程中的肠道萎缩。 方法：通过给新生仔猪置入十二指肠管和颈静脉导管分别给予肠内猪乳和等量营养的PN。其中给予PN亚组以肠内OA50mg/kg/d。 结果：与肠内营养（EN）的对照动物相比，PN可以引起明显的肠道萎缩。OA的治疗对肠道在组织结构上具有明显的保护作用。肠道重量占体重百分比的均数±标准差：EN组为4.30±0.26，PN组为1.92±0.06（P＜0.05，EN比PN），PN＋OA组为3.39±0.79（P＜0.05，PN＋OA比PN）。肠道密度（g/cm）均数±标准差：EN组为0.31±0.03，PN组为0.18±0.03（P＜0.05，EN比PN），PN＋OA组为0.27±0.01（P＜0.05，PN＋OA比PN）。组织病理学结果显示：PN组绒毛/隐窝的比率显著减小，而OA可以明显改善这种情况，比率的均数±标准差v/c：EN组为3.51±0.59，PN组为1.69±0.10（P＜0.05，EN比PN），PN＋OA组为2.90±0.23（P＜0.05，PN＋OA比PN）。与PN和EN组相比，OA治疗组肠道TGR5mRNA的表达显著增加。 结论：胆汁酸激活的G蛋白偶联受体TGR5激动剂OA可以预防PN相关的肠道萎缩。 JPEN J Parenter Enteral Nutr. 2016;40(1):67-72. Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition. Jain AK, Wen JX, Blomenkamp KS, Arora S, Blaufuss TA, Rodrigues J, Long JP, Neuschwander-Tetri BA, Teckman JH. Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri; Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri; Department of Internal Medicine, St Louis University School of Medicine, St Louis, Missouri. BACKGROUND: Nutrition support with parenteral nutrition (PN) is associated with gut atrophy. Prior studies have shown improvement with enteral chenodeoxycholic acid, a dual agonist for the farnesoid X receptor (FXR) and bile acid receptor TGR5. We hypothesized that gut growth is induced by TGR5 activation, and gut atrophy during PN administration could be prevented with the TGR5-specific agonist oleanolic acid (OA). METHODS: Neonatal pigs were implanted with duodenal and jugular vein catheters. Animals were provided equi-nutritious PN or enteral swine milk. A PN subgroup received enteral OA at 50 mg/kg/d. RESULTS: PN caused marked gut atrophy compared with enterally fed (EN) control animals. OA treatment led to preservation of gut mass demonstrated grossly and histologically. The mean ± SD gut weight as a percentage of body weight was 4.30 ± 0.26 for EN, 1.92 ± 0.06 for PN (P < .05, EN vs PN), and 3.39 ± 0.79 for PN+OA (P < .05, PN+OA vs PN). Mean ± SD gut density (g/cm) was 0.31 ± 0.03 for EN, 0.18 ± 0.03 for PN (P < .05 EN vs PN), and 0.27 ± 0.01 for PN+OA (P < .05 PN+OA vs PN). Histologically, a markedly decreased villous to crypt ratio was noted with PN, and OA significantly prevented this decrease. The mean ± SD v/c ratio was 3.51 ± 0.59 for EN, 1.69 ± 0.10 for PN (P < .05, EN vs PN), and 2.90 ± 0.23 for PN+OA (P < .05, PN+OA vs PN). Gut TGR5 messenger RNA expression was significantly elevated with OA treatment compared with both PN and EN. CONCLUSION: The bile acid-activated G protein-coupled receptor TGR5 agonist OA prevented gut atrophy associated with PN. KEYWORDS: gastroenterology; gut atrophy; neonates; oleanolic acid; parenteral nutrition; pediatrics PMID: 25921560 DOI: 10.1177/0148607115583536 |
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