Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model
Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model
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DOI：
10.1016/j.jss.2012.07.053
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发表时间：
2012-12-01
影响因子：
2.2
通讯作者：
Hodges, Steve J.
中科院分区：
文献类型：
--
作者：
Peyton, Charles C.;Keys, Tristan;Hodges, Steve J.
背景：术后粘连形成仍然是一个重要的外科并发症，预防腹盂粘连的方法仍然有限。Halofuginone （HF）是一种1型胶原合成抑制剂，可以增强物理屏障的作用，防止粘连的形成。我们评估了HF注入角蛋白水凝胶在大鼠盲肠磨损模型中预防粘连的有效性。材料与方法：对58只已退休的Sprague Dawley雌性大鼠进行剖腹手术和规范化盲肠磨擦，诱导腹腔内粘连。大鼠随机分为：不治疗组；夹层可吸收附着力屏障；单独角蛋白水凝胶；或角蛋白水凝胶注入22 μ g/mL HF。d-14术后进行尸检，使用标准评分系统评估粘连的程度和强度以及组织学炎症和纤维化的等级。采集血清、肝脏、肾脏和肺部以评估组织HF浓度。生成蛋白和药物洗脱曲线以评估水凝胶中HF的释放。结果：与其他治疗相比，角蛋白- hf水凝胶治疗明显减少了腹部粘连，与Interceed或角蛋白水凝胶单独治疗相比，明显减少了致密粘连。亚组组织学分析未发现质性差异。血清和肾脏中检测不到HF，肝脏和肺中检测到的浓度可以忽略不计。角蛋白- hf水凝胶药物在磷酸盐缓冲溶液（PBS）中的释放持续超过7 d，并与角蛋白降解相关。结论：角蛋白hf水凝胶是一种新型的治疗药物，可以通过物理屏障和药物结合的方法更好地预防术后粘连的发生。(C) 2012爱思唯尔公司版权所有。
Background: 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.Material and methods: 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 mu g/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.Results: 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.Conclusions: 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. (C) 2012 Elsevier Inc. All rights reserved.