类弹性蛋白多肽粘膜下注射在黏膜剥离术中应用的实验研究

Experimental evaluation of elastin-like polypeptides as submucosal injection solution for endoscopic submucosal dissection

摘要:

摘要 ：目的 将类弹性蛋白多肽（elastin-like polypeptides， ELP）作为一种粘膜下注射液应用于内镜下黏膜剥离切除术（endoscopic  submucosal dissection ,ESD），对其有效性进行评估，为临床应用提供依据。方法 54只雄性SD大鼠随机分为三组（n=18）。第一组观察不同注射液分离组织的有效性。根据注射不同的注射剂随机分为三个亚组（n=6），暴露胃后壁分别黏膜下注射ELP，透明质酸钠（SH）和生理盐水（NS）0.2ml，观察并记录药物注射后0min，5min，10min，30min及60min局部粘膜隆起厚度及粘膜表面的改变；第二组观察注射不同注射液后30min黏膜隆起的组织学表现（n=6）；第三组观察黏膜下剥离时不同注射液对出血的影响。根据注射不同注射剂随机分为三个亚组（n=6）。给予上述注射剂处理后，用无菌手术刀片完整切除黏膜下注射后形成的隆起部位，测定粘膜切除20分钟内的出血量。结果 注射药物后60分钟内黏膜隆起厚度比较：ELP组分别与SH和NS组相比差异有统计学意义（P<0.05），即ELP维持黏膜隆起厚度明显大于SH和NS；SH与NS组相比差异有统计学意义（P<0.05），即SH维持黏膜隆起厚度大于NS。组织学观察ELP注射部位的周围组织中未见明显的炎性细胞浸润及坏死。黏膜切除时的出血量：ELP组、SH组、NS组分别为854.±98.9mg、726.3±104.8mg、1144.0±112.4mg， ELP、SH组分别与NS组相比差异有统计学意义（P<0.05）,应用ELP与SH较NS可明显减少出血量。结论 粘膜下ELP后，ELP在黏膜下组织中的弥散明显延缓，在黏膜下形成较持久的液体垫维持粘膜厚度，有利于黏膜组织的剥离切除，并可以减少出血量，因此ELP有可能作为ESD中较为理想的黏膜下注射剂应用于临床。

Abstract:

Abstract: 【Objective】 To explore the effectiveness of elastin-like polypeptides as an ESD submucosal injection solution. 【Methods】 In vivo study, 54 healthy male Sprague-Dawley rats were randomly allocated into there parts (n=18). The first part by submucosal injection of different drugs were randomly divide into three groups (n=6). elastin-like polypeptides (ELP), sodium hyaluronate (SH), nomal saline (NS) 0.2 mL were injected after exposure to the posterior wall of the stomach. Then, to observe and record the increase of mucosal thickness and changes at 0, 5, 10, 30 and 60 minutes. The second part, observe histological appearance of submucosal elevation of each submucosal injection solution at 30 min (n=6). The last part was also randomly divide into three groups (n=6). Remove the lifting mucosal using a surgical blade after injection of above solutions and measure the amount of bleeding from the lesion. 【Results】 The submucosal elevation height using ELP injection was significantly thicker than either SH or NS (P<0.05), whereas SH was thicker than NS. It did not find significant inflammation and damage necrosis of the tissue from the ELP submucosal injection compared with SH and NS. The amount of bleeding was (854.±98.9) mg, (726.3±104.8) mg and (1144.0±112.4) mg for ELP, SH and NS. The group with administration of ELP and SH showed significantly lower values compared with NS (P<0.05). 【Conclusion】 Using ELP as a submucosal injection solution in endoscopic resection could significantly delay dispersion and enable the formation and maintenance of sufficient muscal lesion lifting in this preliminary study. Therefore, ELP might be a promising agent for submucosal injection for ESD, warranting further research and investigation of this innovative technique.