Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition
Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition
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DOI：
10.1177/0148607115583536
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发表时间：
2016-01-01
影响因子：
3.4
通讯作者：
Teckman, Jeffery H.
中科院分区：
文献类型：
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作者：
Jain, Ajay Kumar;Wen, Joy X.;Teckman, Jeffery H.
背景：肠外营养(PN)的营养支持与肠道萎缩有关。先前的研究表明，肠内鹅去氧胆酸可以改善法尼醇X受体(FXR)和胆汁酸受体TGR5的双重激动剂。我们假设肠道生长是由TGR5激活诱导的，而在PN给药过程中，TGR5特异性激动剂齐墩果酸(OA)可以防止肠道萎缩。方法：新生仔猪分别置入十二指肠和颈静脉导管。给动物提供等营养的PN或肠内猪奶。结果：与肠内喂养(EN)对照组相比，PN组大鼠出现明显的肠道萎缩。大体和组织学观察显示，OA治疗可使肠道肿块得以保存。平均+/-SD肠道重量占体重百分比：EN为4.30+/-0.26，PN为1.92+/-0.06(P<；.05，EN vs PN)，PN+OA为3.39+/-0.79(P<；0.05，PN+OA vs PN)。平均+/-SD肠道密度(g/cm)：EN组为0.31+/-0.03，PN组为0.18+/-0.03(P<；0.05)，PN+OA组为0.27+/-0.01(P<；0.05PN+OAvs PN)。组织学上，PN组绒毛与隐窝的比率显著降低，而OA显著阻止了这一下降。平均+/-SDv/c比值：EN为3.51+/-0.59，PN为1.69+/-0.10(P<；.05)，PN+OA为2.90+/-0.23(P<；0.05，PN+OA与PN)。与PN和EN相比，OA处理显著提高了肠道TGR5信使RNA的表达。结论：胆汁酸激活的G蛋白偶联受体TGR5激动剂OA可预防PN相关的肠萎缩。
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.