Botulinum toxin as a treatment for short bowel syndrome in rats

Abstract Purpose: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. Methods: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control). Results: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. Conclusion: This may provide a new promising approach to the surgical treatment of SBS.摘要 **目的**：使用苯扎氯铵（benzalkonium chloride，BAC）对肠道实施去神经支配，可降低短肠综合征（short bowel syndrome，SBS）大鼠的死亡率并改善其体重增长。然而，将这些颇具前景的基础研究成果从实验室转化至临床实践并不可行，因苯扎氯铵可诱发腹膜炎，且会造成不可逆的肠道去神经支配，后续可能伴随内脏的失控性扩张。采用肉毒杆菌毒素（botulinum toxin，BT）替代苯扎氯铵，对短肠综合征大鼠剩余小肠实施去神经支配，或是一项颇具潜力的备选方案，因其可引发温和且短暂的肠道去神经支配。 **方法**：本研究通过检测体重变化与肠道形态学参数，评估了肉毒杆菌毒素对短肠综合征大鼠回肠去神经支配的效果。实验共设置4组，每组6只动物：行肠切除并回肠注射生理盐水组（E组）、行肠切除并回肠注射肉毒杆菌毒素组（EBT组）；对照组为行模拟手术并分别回肠注射肉毒杆菌毒素组（BT组）与生理盐水组（C组，对照组）。 **结果**：观察显示，对剩余回肠施以肉毒杆菌毒素治疗，可完全逆转广泛小肠切除术后伴随的体重下降。 **结论**：该研究或为短肠综合征的外科治疗提供全新的颇具前景的方案。