Meng Ke, Shen Lei, Li Yan, Wen Jing, Liu Qingsen, Zhang Xiaomei
Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Gastroenterology and Hepatology, 984 Hospital, Beijing, China.
J Thorac Dis. 2022 Mar;14(3):668-678. doi: 10.21037/jtd-22-202.
Benign esophageal strictures are common in clinical practice. The commonly used methods for preventing benign esophageal strictures still have many shortcomings. In this study, we investigated the preventive effect and possible mechanism of endoscopic local injection of botulinum toxin type A (BTX-A) on scarring esophageal stricture caused by electrocautery in rabbit models, with an attempt to provide a theoretical basis for the clinical application of BTX-A in the prevention of benign esophageal stricture.
Adult male New Zealand rabbits were randomly divided into 4 groups: cautery group (cauterized with 30 W electrocoagulation power without other intervention), saline group (injected with normal saline at 4 spots in the local esophagus after modeling), BTX-A I group (injected with 10 U of BTX-A after modeling), and BTX-A II group (injected with 20 U of BTX-A after modeling). Body weight was measured at postoperative weeks 1, 2, and 4. Esophagography was performed, and the internal diameter of the esophagus was measured. The esophageal tissues were harvested for hematoxylin and eosin (HE) staining and Masson staining. Type I, type III collagen levels and the mRNA expression of transforming growth factor β1 (TGF-β1) in esophageal tissues were detected.
Compared with the cautery and saline groups, the BTX-A I and BTX-A II groups had significantly higher body weight, larger esophageal internal diameter, lower type I and type III collagen levels, and lower TGF-β1 mRNA expression levels in esophageal tissues at postoperative week 4. Comparisons between the BTX-A I and BTX-A II groups showed no significant differences in terms of body weight, esophageal internal diameter, and type I collagen level at postoperative week 4. However, the BTX-A II group had a significantly lower type III collagen level and TGF-β1 mRNA expression level than the BTX-A I group.
Local injection of BTX-A can alleviate esophageal stricture after electrocautery and has a preventive effect on benign esophageal stricture caused by electrocautery in rabbits. The mechanism may be that BTX-A down-regulates the expression of TGF-β1 in the esophageal tissue at the burn site and reduces the deposition of collagen.
良性食管狭窄在临床实践中很常见。常用的预防良性食管狭窄的方法仍存在许多缺点。在本研究中，我们研究了内镜下局部注射A型肉毒杆菌毒素（BTX-A）对兔模型中电灼所致瘢痕性食管狭窄的预防作用及可能机制，试图为BTX-A在预防良性食管狭窄中的临床应用提供理论依据。
成年雄性新西兰兔随机分为4组：电灼组（以30W电凝功率进行电灼，无其他干预）、生理盐水组（建模后在食管局部4个点注射生理盐水）、BTX-A I组（建模后注射10U BTX-A）和BTX-A II组（建模后注射20U BTX-A）。在术后第1、2和4周测量体重。进行食管造影，并测量食管内径。采集食管组织进行苏木精-伊红（HE）染色和Masson染色。检测食管组织中I型、III型胶原水平及转化生长因子β1（TGF-β1）的mRNA表达。
与电灼组和生理盐水组相比，BTX-A I组和BTX-A II组在术后第4周体重显著增加，食管内径增大，食管组织中I型和III型胶原水平降低，TGF-β1 mRNA表达水平降低。BTX-A I组和BTX-A II组在术后第4周体重、食管内径和I型胶原水平方面比较无显著差异。然而，BTX-A II组的III型胶原水平和TGF-β1 mRNA表达水平显著低于BTX-A I组。
局部注射BTX-A可减轻电灼后食管狭窄，对兔电灼所致良性食管狭窄有预防作用。其机制可能是BTX-A下调烧伤部位食管组织中TGF-β1的表达，减少胶原沉积。
