应用猪小肠粘膜下层预防内镜粘膜下剥离术后食管狭窄的动物研究

发布时间：2018-10-12 19:38

【摘要】：研究背景内镜黏膜下剥离术(endoscopic submucosal dissection,ESD)是早期食管癌有效的治疗方法。但ESD术可能会造成严重的食管狭窄,影响患者的预后及生活治疗。小肠黏膜下层(small intestinal submucosa,SIS)是一种理想细胞外基质(extracellular matrix,ECM)材料,其具有高组织相容性及生物力学性能,安全性高。目的探讨猪小肠细胞外基质预防ESD术后狭窄的功效。方法选取9只杂交猪在插管麻醉后行环周食管ESD术。其中3只在内镜下用支架将小肠细胞外基质放置到食管ESD术后食管损伤位置为小肠粘膜下层组,3只在创面放置支架为支架组,另外3只为空白对照组。在第2周及第4周复查胃镜观察食管狭窄情况,在第8周进行病理学评价。结果通过十二烷基硫酸钠脱细胞法和酶消化方法后,苏木精-伊红染色法(hematoxylin and eosin stain)检测发现脱细胞成功,从而制备了具有组织相容性的猪小肠细胞外基质。9只杂交猪接受环周食管ESD术后,支架组及空白对照组的6只猪在术后2周发生了不同程度的粘膜狭窄,其中3只因不能耐受经口进食,而进行了早期安乐死。2周及4周性内镜检查,可见支架组及空白对照组ESD术后创面出现持续的炎症反应及不完全的上皮形成。猪小肠黏膜下层组行2周及4周性内镜检查,发现ESD术后创面炎症反应少,能逐渐形成上皮组织,食管狭窄程度较支架组及空白对照组低。4周时病理标本显示,猪小肠黏膜下层组的标本粘膜炎症反应少,狭窄程度较支架组及空白对照组低。结论本研究成功制备具有生物相容性的猪小肠细胞外基质,将其放置在猪食管环周ESD术后的创面,有效预防了食管狭窄的发生。通过本研究将有助于为临床预防ESD术后食管狭窄提供新思路,并为组织工程生物材料的制备及临床应用夯实基础。
[Abstract]:Background Endoscopic submucosal dissection (endoscopic submucosal dissection,ESD) is an effective treatment for early esophageal cancer. However, ESD may cause severe esophageal stenosis, affecting the prognosis of patients and life treatment. Small intestinal submucosal (small intestinal submucosa,SIS is an ideal extracellular matrix (extracellular matrix,ECM) material with high histocompatibility, biomechanical properties and high safety. Objective to investigate the effect of extracellular matrix (ECM) of porcine small intestine on prevention of stenosis after ESD. Methods Nine crossbred pigs were treated with circumferential esophageal ESD after intubation anesthesia. Three of them were placed in the submucous layer of small intestine group, three of them were stents on the wound surface, and the other three were the blank control group, when the extracellular matrix of small intestine was placed in the esophageal submucosa group after esophageal ESD operation. Esophageal stenosis was observed by gastroscopy at week 2 and week 4, and pathological evaluation was performed at week 8. Results after decellularization of sodium dodecyl sulfate and enzyme digestion, (hematoxylin and eosin stain) detection of hematoxylin and eosin staining showed that acellular cells were successfully removed. The extracellular matrix of pig small intestine with histocompatibility was prepared. Nine crossbred pigs received circumferential esophageal ESD. Six pigs in the stent group and the blank control group suffered from mucosal stenosis in different degrees at 2 weeks after operation. Three of them underwent early euthanasia because they could not tolerate oral feeding. 2 and 4 weeks of endoscopic examination showed persistent inflammatory reaction and incomplete epithelium formation in the wounds after ESD in the stent group and the blank control group. After 2 and 4 weeks of endoscopic examination in the porcine intestinal submucosa group, it was found that the inflammatory reaction of the wound surface after ESD was less and the epithelial tissue was gradually formed. The degree of esophageal stenosis was lower than that in the stent group and the blank control group. The mucosal inflammation in the submucosal group was less and the degree of stenosis was lower than that in the stent group and blank control group. Conclusion in this study, the biocompatible extracellular matrix of porcine small intestine was successfully prepared and placed in the wound of porcine periesophageal circumferential ESD, which effectively prevented the occurrence of esophageal stenosis. This study will provide a new idea for clinical prevention of esophageal stenosis after ESD and lay a solid foundation for the preparation and clinical application of tissue engineering biomaterials.
【学位授予单位】：首都医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

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