Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Pediatric Surgery University of Texas Medical School at Houston, Houston, Texas, USA.
Neurogastroenterol Motil. 2020 Jul;32(7):e13834. doi: 10.1111/nmo.13834. Epub 2020 Mar 12.
Gastrointestinal (GI) dysfunction is observed clinically after spinal cord injury (SCI) and contributes to the diminished long-term quality of life. Our study examined the acute and chronic GI vascular changes that occur following SCI. We demonstrated that the GI vascular tract in SCI mice becomes compromised during the acute phase of injury and persists into the chronic phase of injury.
Gastrointestinal vasculature permeability was measured using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) at 48 hours, and 2 and 4 weeks following contusion spinal cord injury. Angiopoietin-1, a vascular stabilizing protein, was administered intravenously following injury. Intestinal contractile activity assessments were performed following the last imaging session.
Our results indicated that a single administration of Ang-1 reduced vascular permeability at 48 hours but the effect was only transient. However, when the treatment paradigm was changed from a single administration to multiple administrations of Ang-1 following contusion injury, our DCE MRI data indicated a significant decrease in GI vascular permeability 4 weeks after injury compared with vehicle control treated animals. This improved GI vascular permeability was associated with improved sustained intestinal contractile activity. We also demonstrated that Ang-1 reduced the expression of sICAM-1 in the ileum compared with the saline-treated group.
We show that the GI vasculature is compromised in the acute and chronic phase of injury following spinal contusion. Our results also indicate that multiple administrations of Ang-1 can attenuate GI vascular permeability, possibly reduce inflammation, and improve sustained agonist-induced contraction compared with saline treatment.
脊髓损伤（SCI）后临床上观察到胃肠道（GI）功能障碍，这导致长期生活质量下降。我们的研究检查了 SCI 后发生的急性和慢性胃肠道血管变化。我们证明，SCI 小鼠的胃肠道血管在损伤的急性期受损，并持续到损伤的慢性期。
使用动态对比增强磁共振成像（DCE MRI）在挫伤性脊髓损伤后 48 小时、2 周和 4 周测量胃肠道血管通透性。血管稳定蛋白血管生成素 1（Ang-1）在损伤后静脉内给药。在最后一次成像后进行肠收缩活动评估。
我们的结果表明，单次给予 Ang-1 可降低 48 小时的血管通透性，但作用是短暂的。然而，当治疗方案从损伤后单次给予 Ang-1 改为多次给予 Ang-1 时，我们的 DCE MRI 数据表明，与接受载体对照治疗的动物相比，损伤后 4 周胃肠道血管通透性显著降低。这种改善的胃肠道血管通透性与持续的肠收缩活动改善有关。我们还证明，与盐水处理组相比，Ang-1 降低了回肠中 sICAM-1 的表达。
我们表明，在脊髓挫伤后的急性和慢性损伤阶段，胃肠道血管受损。我们的结果还表明，多次给予 Ang-1 可减轻胃肠道血管通透性，可能减轻炎症，并改善与盐水治疗相比持续激动剂诱导的收缩。
