Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles and USC Keck School of Medicine, Los Angeles, California.
Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles and USC Keck School of Medicine, Los Angeles, California; Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
J Surg Res. 2020 Nov;255:86-95. doi: 10.1016/j.jss.2020.05.052. Epub 2020 Jun 15.
Short bowel syndrome (SBS) is a condition that results from inadequate intestinal absorptive capacity, usually after the loss of functional intestine. We have previously developed a severe model of SBS in zebrafish that demonstrated increased intestinal adaptation (IA) and epithelial proliferation in SBS zebrafish. However, many children with SBS do not have this extreme intestinal loss. Therefore, in this study, we developed a variation of this model to evaluate the effects of increasing intestinal length on IA and the complications of SBS.
After Institutional Animal Care and Use Committee approval, adult male zebrafish were assigned to three groups: sham (n = 30), S1-SBS (n = 30), and S3-SBS (n = 30). Sham surgery included ventral laparotomy alone. S1-SBS surgery consisted of laparotomy with creation of a proximal stoma at S1 (jejunostomy equivalent) and ligation at S4. S3-SBS surgery had stoma creation at S3 (ileostomy equivalent) and the same ligation. Fish were harvested at 14 d. Markers of IA were measured from proximal intestinal segments, and the liver was analyzed for development of hepatic steatosis.
At 14 d, S3-SBS fish lost less weight than S1-SBS and had increased markers of IA compared with sham fish, which were decreased compared with S1-SBS fish. S3-SBS fish had decreased proximal intestinal inflammation compared with S1-SBS fish. S1-SBS fish developed extensive hepatic steatosis. Although S3-SBS fish have increased hepatic steatosis compared with sham fish, it is decreased compared with S1-SBS.
Longer remnant intestine decreases the extent of IA, inflammation, and hepatic steatosis in a zebrafish model of SBS.
短肠综合征（SBS）是一种由于肠道吸收能力不足而导致的疾病，通常是在功能性肠丢失后发生。我们之前在斑马鱼中开发了一种严重的 SBS 模型，该模型显示 SBS 斑马鱼的肠道适应性（IA）和上皮细胞增殖增加。然而，许多 SBS 患儿没有这种极端的肠道损失。因此，在这项研究中，我们开发了这种模型的变体，以评估增加肠道长度对 IA 和 SBS 并发症的影响。
在机构动物护理和使用委员会批准后，成年雄性斑马鱼被分为三组：假手术组（n=30）、S1-SBS 组（n=30）和 S3-SBS 组（n=30）。假手术仅包括腹部切开术。S1-SBS 手术包括剖腹术，在 S1 处创建近端造口（空肠吻合术等效物）并在 S4 处结扎。S3-SBS 手术在 S3 处创建造口（回肠造口术等效物）并进行相同的结扎。鱼在 14 天时收获。从近端肠段测量 IA 的标志物，并分析肝脏以确定肝脂肪变性的发展。
在 14 天时，S3-SBS 鱼的体重减轻比 S1-SBS 少，与 sham 鱼相比，IA 的标志物增加，与 S1-SBS 鱼相比则减少。S3-SBS 鱼的近端肠炎症较 S1-SBS 鱼减少。S1-SBS 鱼发生广泛的肝脂肪变性。尽管 S3-SBS 鱼的肝脂肪变性较 sham 鱼增加，但与 S1-SBS 鱼相比则减少。
在 SBS 的斑马鱼模型中，较长的残留肠减少了 IA、炎症和肝脂肪变性的程度。
