Developing a Novel Ambulatory Total Parenteral Nutrition-Dependent Short Bowel Syndrome Animal Model
Developing a Novel Ambulatory Total Parenteral Nutrition-Dependent Short Bowel Syndrome Animal Model
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DOI：
10.1016/j.jss.2018.08.042
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发表时间：
2019-02-01
影响因子：
2.2
通讯作者：
Jain, Ajay Kumar
中科院分区：
文献类型：
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作者：
Price, Amber;Blomenkamp, Keith;Jain, Ajay Kumar
背景：短肠综合征（SBS）是由广泛的肠切除引起的。 SBS 患者需要全肠外营养 (TPN) 才能生存。了解 TPN 相关肝损伤和肠道萎缩的机制对于开发 SBS 疗法至关重要。现有的使用拴系动物的 SBS 模型有很大的局限性，并且与流动的人类 SBS 患者不同。我们假设我们可以在仔猪中诱导 SBS 并开发动态 TPN-SBS 模型。材料和方法：18 只新生猪接受十二指肠和颈静脉导管。它们配备了装有 TPN 的夹克和微型泵。六头仔猪接受了 90% 的小肠切除和导管放置（SBS 组）。非 SBS 仔猪被随机分配至肠内营养 (EN) 或 TPN。结果：SBS 动物成功完成肠切除。所有组的体重增加相似。与 EN 相比，SBS 动物的血清胆红素增加。 EN 的平均结合胆红素 +/- SD 为 0.045 +/- 0.01（P = 0.03 EN 对比 TPN，P = 0.03 SBS 对比 EN），TPN 为 1.09 +/- 1.25（P = 0.62 TPN 对比 SBS）。与 EN 和 SBS 组相比，TPN 组的肠道密度降低。 TPN 的平均肠道密度 +/- SD 为 0.11 +/- 0.04（P = 0.0004 TPN 与 SBS 和 P = 0.00007 TPN 与 EN），EN 与 SBS 没有统计学差异（P = 0.32）。结论：我们使用仔猪创建了一种新型的流动 TPN-SBS 模型，模仿人类 SBS 患者的长期 TPN 给药。我们的模型证明了 TPN 相关的结合性高胆红素血症和代偿性肠道肥大，正如 SBS 人类中所注意到的那样。该模型对于未来的研究具有巨大的潜力。 (C) 2018 Elsevier Inc. 保留所有权利。
Background: Short bowel syndrome (SBS) results from extensive bowel resection. Patients with SBS require total parenteral nutrition (TPN) for survival. Understanding mechanisms contributing to TPN- associated liver injury and gut atrophy are critical in developing SBS therapies. Existing SBS models using tethered animals have significant limitations and are unlike ambulatory human SBS patients. We hypothesized that we could induce SBS in piglets and develop an ambulatory TPN-SBS model.Material and methods: Eighteen neonatal pigs received duodenal and jugular catheters. They were fitted with a jacket holding TPN and a miniaturized pump. Six piglets had 90% small bowel resection and catheter placement (SBS group). Non-SBS piglets were randomized into enteral nutrition (EN) or TPN.Results: Bowel resection was successfully accomplished in SBS animals. Weight gain was similar in all groups. SBS animals had increased serum bilirubin compared to EN. Mean conjugated bilirubin +/- SD was 0.045 +/- 0.01 for EN, (P = 0.03 EN versus TPN and P = 0.03 SBS versus EN) and 1.09 +/- 1.25 for TPN, (P = 0.62 TPN versus SBS). Gut density was reduced in the TPN group compared to EN and SBS groups. Mean gut density +/- SD was 0.11 +/- 0.04 for TPN (P = 0.0004 TPN versus SBS and P = 0.00007 TPN versus EN) and not statistically different for EN versus SBS (P = 0.32).Conclusions: We created a novel, ambulatory TPN-SBS model using piglets, mimicking long-term TPN delivery in human SBS patients. Our model demonstrated TPN-related conjugated hyperbilirubinemia and compensatory gut hypertrophy, as noted in humans with SBS. This model holds great potential for future research. (C) 2018 Elsevier Inc. All rights reserved.