类弹性蛋白多肽黏膜下注射在内镜黏膜下剥离术中的应用研究

Comparison of different concentrations of elastin-like polypeptides for endoscopic submucosal dissection

目的 研究类弹性蛋白多肽（ELP）作为一种黏膜下注射制剂在内镜黏膜下剥离术（ESD）中的应用,比较不同质量浓度的ELP在ESD中的应用,并对其有效性和安全性进行评估.方法 40只新西兰大白兔随机分为2组（n=20）.第1组观察不同注射液分离组织的有效性.依据不同质量浓度的ELP（0.05、0.025、0.012 5、0.005 g/ml）及对照组（甘油果糖）随机分为5个亚组（n=4）,切取胃组织,在胃窦或胃体处分别注射不同质量浓度的ELP和甘油果糖2ml,观察并记录药物注射后0、5、10、30 min局部黏膜隆起高度及黏膜表面的改变.第2组测量不同注射液的注射压力.亚组分组同第1组,使用注射器/压力计组件分别测量2ml不同质量浓度ELP和甘油果糖的注射压力.结果 注射药物后30 min内,0.05、0.025 g/ml ELP维持黏膜隆起高度均大于甘油果糖,差异具有统计学意义（P＜0.05）;0.012 5 g/ml ELP维持黏膜隆起高度与甘油果糖相比,差异无统计学意义（P＞0.05）;0.005 g/ml ELP维持黏膜隆起高度小于甘油果糖,且差异具有统计学意义（P＜0.05）.同时,注射压力与浓度相关,2 ml ELP（0.05、0.025、0.012 5、0.005 yml）和甘油果糖注射后的平均注射压力分别为（332±36）、（223±24）、（174±22）、（142±19）、（269±17）kPa,0.025 g/ml ELP注射压力小于甘油果糖,差异有统计学意义（P＜0.05）.结论 ELP是一种安全有效的新型黏膜下注射制剂,推荐ESD术中注射ELP的最适质量浓度为0.025 g/ml.

Objective To compare the effectiveness and safety of different concentrations of elastin-like polypeptides （ELP） as novel submucosal injection material for endoscopic submucosal dissection.Methods Forty healthy New Zealand white rabbits were randomly divided into two groups （n=20）.The first group by submucosal injection of different drugs were randomly divide into five groups （n=4）.Four concentrations of 50 ku ELP （0.05,0.025,0.012 5,0.005 g/ml） were used separately in each group,while glycerin fructose was used for control group.Each solution （2 ml） was injected into the submucosa through the resected margin,the increase of mucosal thickness and surface changes were observed and recorded at 0,5,10,and 30 min.The subgroup by submucosal injection of different drugs were randomly divide into five groups （n=4）.The injection pressure of each solution （2 ml） with the 25-gauge needle was calculated by a manometer,which was connected between the needle and syringe.Results The submucosal uplift heights in groups using the 0.05 g/ml ELP and 0.025 g/ml ELP injection were significantly thicker than that of glycerin fructose （P〈0.05）,the 0.012 5 g/ml ELP and glycerin fructose injection showed no significant difference （P〉0.05）,whereas the uplift height in glycerin fructose group was thicker than that of the 0.005 g/ml ELP （P〈0.05）.The injection pressure correlated with the ELP concentration.The injection pressures of 0.05,0.025,0.012 5,0.005 g/ml ELP solutions were （332±36） kPa,（223±24） kPa,（174±22） kPa and （142±19） kPa,respectively,and that of glycerin fructose was （269±17） kPa.The 0.025 g/ml ELP solution was easily injected into the porcine stomach to create submucosal uplift.The injection pressure of the 0.025 g/ml ELP solution showed significantly lower value compared with that of glycerin fructose （P〈0.05）.Conclusions ELP might be a promising agent for submucosal injection for endoscopic submucosal dissection （ESD）,and 0.025 g/ml ELP might be efficient concentration for maintaining mucosal elevation,injection pressure and safety.