Department of Urology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA.
J Surg Res. 2012 Dec;178(2):545-52. doi: 10.1016/j.jss.2012.07.053. Epub 2012 Aug 10.
Postoperative adhesion formation continues to be a significant surgical complication, and methods for preventing abdominopelvic adhesions remain limited. Halofuginone (HF) is a type-1 collagen synthesis inhibitor and may enhance the effects of a physical barrier in preventing adhesion formation. We evaluated the effectiveness of a HF infused keratin hydrogel on preventing adhesions in a rat cecal abrasion model.
Laparotomy and standardized cecal abrasion was performed on 58 retired-breeder Sprague Dawley female rats to induce intra-abdominal adhesions. Rats were randomized to: no treatment; Interceed absorbable adhesion barrier; keratin hydrogel alone; or keratin hydrogel infused with 22 μg/mL of HF. Necropsies were performed at postop d-14 to assess the extent and tenacity of adhesions and grade histologic inflammation and fibrosis using a standard scoring system. Serum, liver, kidneys, and lungs were harvested to evaluate tissue HF concentrations. Protein and drug elution curves were generated to assess the release of HF from the hydrogel.
Treatment with Keratin-HF hydrogel resulted in significantly fewer abdominal adhesions than any other treatment, and significantly less dense adhesions compared with Interceed or keratin hydrogel alone. Subset histologic analysis did not reveal qualitative differences. HF was undetectable in serum and kidneys, and detected at negligible concentrations in liver and lungs. Keratin-HF hydrogel drug release in phosphate-buffered solution (PBS) was sustained over 7 d and correlated with keratin protein degradation.
Keratin-HF hydrogel is a novel therapeutic agent that may provide a better method for preventing the development of postoperative adhesions using a combined physical barrier and pharmacologic approached.
术后粘连形成仍然是一种严重的手术并发症，预防腹盆腔粘连的方法仍然有限。卤夫酮（HF）是一种 1 型胶原合成抑制剂，可能增强物理屏障在预防粘连形成中的作用。我们评估了 HF 浸渍角蛋白水凝胶在预防大鼠盲肠擦伤模型粘连中的效果。
对 58 只退休种鼠进行剖腹术和标准化盲肠擦伤，以诱导腹腔内粘连。大鼠随机分为：无治疗；可吸收防粘连屏障；角蛋白水凝胶单独使用；或角蛋白水凝胶中注入 22μg/mL HF。术后第 14 天进行尸检，以评估粘连的程度和粘连的坚固性，并使用标准评分系统评估组织炎症和纤维化的程度。采集血清、肝脏、肾脏和肺脏，以评估组织 HF 浓度。生成蛋白质和药物洗脱曲线，以评估 HF 从水凝胶中的释放情况。
与其他任何治疗方法相比，角蛋白-HF 水凝胶治疗导致的腹部粘连明显减少，与单独使用可吸收防粘连屏障或角蛋白水凝胶相比，粘连密度明显降低。亚组组织学分析没有显示出定性差异。HF 在血清和肾脏中无法检测到，在肝脏和肺部中仅检测到可忽略不计的浓度。角蛋白-HF 水凝胶在磷酸盐缓冲液（PBS）中的药物释放可持续 7 天以上，并与角蛋白蛋白降解相关。
角蛋白-HF 水凝胶是一种新型治疗剂，可能为使用物理屏障和药物联合方法预防术后粘连的发展提供更好的方法。
