Arbell Dan, Udassin Raphael, Koplewitz Benjamin Z, Ohana Meir, Genina Olga, Pines Mark, Nagler Arnon
Department of Pediatric Surgery, Hadassah University Hospital, Kyriat Hadassah, PO Box 12000, 91120 Jerusalem, Israel.
Laryngoscope. 2005 Sep;115(9):1632-5. doi: 10.1097/01.mlg.0000176551.09051.f2.
Esophageal strictures caused by caustic injury continue to be a plaguing problem. Halofuginone (HF) has been proven to inhibit the formation of fibrosis in various animal models and human diseases. Its mechanism appears to be through the suppression of the production of collagen alpha1(I) and transforming growth factor-beta signaling pathway. We tried to assess whether HF would have an effect on the formation of strictures after inducing caustic esophageal.
Esophageal injury was caused by injecting 25% NaOH to an isolated esophageal segment. Study group rats were treated with HF orally for 3 consecutive days before the injury and afterward. Control group rats received regular chow. The results were evaluated by upper gastrointestinal series (UGI) and through pathologic studies.
HF treatment resulted in marked improvement in the esophageal strictures. The UGI series showed esophageal patency of 73% (45%-100%) in the treated animals (n = 7) as compared with almost no patency, 11% (5-16%), in the controls (n = 4) (P = .018). The histologic examination showed significantly less stricture and scarring in the treated group. Whereas the ratio between the esophageal wall thickness to mucosal thickness was 2.34 +/- 0.23 in the study group, the control group had a ratio of 9.56 +/- 0.69 (P = .0044). Finally, whereas 86% of the study group survived, all the rats in the control group died by day 20.
HF modulated the wound healing reaction caused by caustic injury of the esophagus in a rat model, resulting in increased esophageal patency, reduction in esophageal wall thickness, and increased survival.
苛性损伤所致食管狭窄仍是一个棘手的问题。已证实常山酮（HF）可抑制多种动物模型和人类疾病中纤维化的形成。其机制似乎是通过抑制Ⅰ型胶原α1的产生和转化生长因子-β信号通路。我们试图评估HF对苛性食管损伤后狭窄形成是否有影响。
通过向离体食管段注射25%氢氧化钠造成食管损伤。研究组大鼠在损伤前及损伤后连续3天口服HF。对照组大鼠给予常规食物。通过上消化道造影（UGI）和病理研究评估结果。
HF治疗使食管狭窄有显著改善。UGI造影显示，治疗组动物（n = 7）食管通畅率为73%（45%-100%），而对照组（n = 4）几乎无通畅，通畅率为11%（5%-16%）（P = 0.018）。组织学检查显示治疗组狭窄和瘢痕形成明显减少。研究组食管壁厚度与黏膜厚度之比为2.34±0.23，而对照组为9.56±0.69（P = 0.0044）。最后，研究组86%存活，而对照组所有大鼠在第20天死亡。
在大鼠模型中，HF调节了食管苛性损伤引起的伤口愈合反应，导致食管通畅性增加、食管壁厚度减小和存活率提高。
