下食管括约肌球囊扩张建立咽喉反流性疾病兔模型

目的探讨通过下食管括约肌(lower esophageal sphincter,LES)扩张建立咽喉反流性疾病(laryngophyngeal reflux disease,LPRD)模型的可行性。方法18只新西兰白兔随机分为实验组10只和对照组8只,对实验组动物进行LES测压定位后,使用球囊对LES进行注水扩张,对照组同法置入球囊,但不进行球囊注水。扩张前1周及扩张后2周行咽喉及食管下段pH监测,LES平均静息压检测;扩张前1周、扩张后2周及8周行喉镜检查,进行喉镜下反流体征评分;扩张后8周处死动物,对其喉部及食管下段黏膜取材,光镜下观察其病理变化。结果扩张后pH监测验证实验组造模成功8只(80.0%,8/10),实验组扩张前咽喉酸反流时间百分比(%)、反流事件数(次)、反流最长时间(s)分别为0(0,0)、0(0,0)、0(0,0),扩张后分别为17.5(8.2,29.4)、3(1,5.5)、17.2(10.2,30.8),较扩张前增加,差异有统计学意义(P<0.01)。实验组扩张前食管下段pH监测酸反流时间百分比、反流事件数、反流最长时间分别为0(0,0.7)、0(0,1)、0(0,1.2),扩张后分别为23.1(4.8,49.5)、3(1,6)、25.9(11.5,56.8),较扩张前增加,差异有统计学意义(P<0.01)。实验组扩张前LES压力28.0±5.6 mmHg,较扩张后(17.2±3.3 mmHg)升高,差异有统计学差异(P=0.001);实验组扩张前RFS评分3.1±1.2分,扩张后2周为3.6±1.4分,扩张后8周为8.6±2.5分,扩张前和扩张后2周差异无统计学意义(P=0.482),但扩张前与扩张后8周差异有统计学意义(P=0.005)。病理检查示实验组喉部及食管黏膜均可观察到不同程度慢性炎症。结论食管下括约肌球囊扩张可安全、有效地建立LPRD动物模型。

Experimental Study on the Establishment of A Rabbit Model of Laryngopharyngeal Reflux Disease by Balloon Dilation

Objective To explore the feasibility of establishing laryngopharyngeal reflux disease(LPRD)rabbit model through lower esophageal sphincter(LES)dilation.Methods A totat of 18 New Zealand rabbits were randomly divided into two groups,10 in the experimental group and 8 in the control group.Balloon dilatation was carried out in experimental group to reproduce the animal model of LPRD after the LES positioning.The esophageal manometry and esophageal pH monitoring were performed in all animals 1 week before and 2 weeks after dilation,and the mean LES pressure before and after the dilation was compared.PH monitoring of the larynx and lower esophagus was performed 1 week before and 2 weeks after dilation.If no laryngeal reflux event was detected,further dilation was performed.Laryngoscopy was performed 1 week before dilatation,2 weeks and 8 weeks after dilatation to compare the reflux founding score(RFS)at each time point.The pathological findings of larynx and esophagus 8 weeks after dilatation were compared with those in the control group.Results Laryngopharyngeal reflux was detected in 8 animals and the achievement ratio in reproducing LPRD model was 80%.pH monitoring showed that the laryngopharyngeal reflux time percentage,total reflux number and longest reux time in the experimental group before dilation were 0(0,0),0(0,0),0(0,0),respectively,and after dilation were 17.5(8.2,29.4),3(1,5.5),and 17.2(10.2,30.8),respectively,which were significantly higher than those before dilation(P<0.01).pH monitoring of lower esophagus showed that reflux time percentage,total reflux number and longest reux time in the experimental group before dilation were 0(0,0.7),0(0,1),0(0,1.2),respectively and after dilation were 23.1(4.8,49.5),3(1,6),25.9(11.5,56.8),respectively,which were significantly higher than those before dilation(P<0.01).There was a significant difference between the LES pressure before dilatation and that after dilatation(28.0±5.6)mmHg vs(17.2±3.3)mmHg,P=0.001].RFS of the experimental group was 3.1±1.2 one week before dilatation,3.6±1.4 two weeks after dilatation,and 8.6±2.5 eight weeks after dilatation,compared with RFS of the animals before dilatation,there was no statistically significant difference between the 2 weeks after(P=0.482),but there was a statistically significant difference between the 8 weeks after(P=0.005).Compared with the control group under microscope,chronic inflammation of different degrees could be observed in both laryngeal and esophageal mucosa of the experimental group.Conclusion Balloon dilation of LES is a safe and effective method to establish the animal model of LPRD.