| Background:In Europe and the United States,GERD(Gastroesophageal reflux disease,GERD)related Barrett’s esophagus(Barrett’s esophagus,BE) and esophageal adenocarcinoma(Esophageal adenocarcinoma,EAC) have a high mobidity.With the rapid development of economy in China, dramatic changes occur in the lifestyle and the diet of urban and rural residents,and the mobidity of BE and EAC is also on the rise in recent years. BE is attracting people’s attention as an important risk factor of esophageal adenocarcinoma. Animal models, as an important tool for studying human disease, can be used to study the etiology, pathology phenotype,pathogenesis and methods of prevention and treatment. Therefore,we have established BE and EAC models with different operative methods,and its advantages and disadvantages are evaluated,as well as its value to human studies. Different animal models serve different research purposes,but any animal model has its inherent limitations. Therefore,selecting and establishing an appropriate animal model is very important to study BE and EAC.Rat is one of the most commonly used animals in BE and EAC studies. The esophagus of rat has a moderate size,and the operation on it is relatively easy. Multilayered epithelium, BE and EAC can be stimulated by the gastroesophageal reflux liquid due to its greater susc- eptibility.Objective:To establish animal model of Barrett’s esophagus with different operative methods in order to evaluate the development and progression of Barrett’s esophagus study,which can provide a theoretical basis for prevention and treatment of Barrett’s esophagus in the future.Methods:1 Experimental animals:160 male healthy clean SD rats,weighing(200± 10)g,were fed in cages,five per cage.Before feeding,breeding room was expo- sed to ultraviolet light for disinfection,and cages were given peracetic acid for disinfection.A constant temperature of(22±2)℃ and humidity of 50% to 60% were maintained indoor. Light and dark was alternating each 12 h. Rats were given one week to adapt to the environment,and were fed with the standard pellets and tap water.2 Grouping:160 male SD rats were randomly divided into A,B,C,D,E,F group.Group A:sham operation group(SO group,n=10);Group B: esophago- jejunal anastomosis group(EJA group,n=30);Group C:esophagus duodenum side anastomosis group(EDA group,n=30);Group D:Esophageal duodenum side anastomosis plus iron group(EDA+Fe group,n=30);Group E:esophagus duodenum side to side anastomosis groups(referred EGDA group,n=30); Group F:Esophageal duodenal iron plus side to side anastomosis group(EGDA+Fe group,n=30).3 Animal models making:Before operation rats were fasted and water deprived for 24 h and 12 h, respectively.Rats were intraperitoneally anaesthe- tized with 10% chloral hydrate(0.3ml/100g).Abdominal median incision was chosen to open the abdominal cavity.Gastrojejunostomy esophageal reflux, gastroduodenal esophageal reflux and jejunum esophageal reflux rat models were established by esophagojejunostomy anastomosis, esophagoduodenal anastomosis and esophagogastrodudenal anastomosis,respectively.Sham group was the control group.Group D and F were intraperitoneal injected with iron dextran injection(30mg/kg,twice a week for 30 weeks)after 2 weeks.After 12 weeks 5 rats were sacrificed in each group, the remaining were killed after 32 weeks.The lower esophageal segment was taken for gross pathological observation and light microscope after HE staining.Results:1 Gross morphology changes of esophagus in rats Five rats were sacrificed after 12 weeks in each group.In group A,there were no peritoneal adhesions.The esophagus had a normal appearance and a smooth mucosa when Being cut longitudinally,and no swelling,erosion or ulceration. Inflammation occurred in all the other groups.There were mucosal congestion, erosion,scattered superficial ulcers and longitudinal deep ulcers in the lower part of the esophagus.It was more serious in group D and F,and there were different degrees of peritoneal adhesions.Esophageal lesions were worse after 32 weeks compared with those after 12 weeks.The appearance of esophagus was significantly enlarged. The case got even worse in group D and F.There were severe peritoneal adhesions,reduced stomach volume and white pebble- like mass at the bottom of the stomach.2 The model of tissue pathological changes esophageal inflammation was seen in group B,C,D,E and F after 12 weeks.Inflammation was acute and/or chronic,which was mainly acute mostly accompanied by neutrophil infiltration and tissue edema.There was dysplasia of esophageal squamous epithelium, which showed an appearance of papilloma.The esophageal wall was thicke- ning with different levels of basal cell hyperplasia.Esophageal lesions, inflammation and ulceration got worse after 32 weeks, compared with those after 12 weeks. The incidence of inflammation was 100 percent in group B,C, D,E and F.The basal cell layer got thicker than Before.Epithelial papilla was extended with the basal cell hyperplasia. In group B,C,D,E and F the incid- ence of squamous dysplasia was respectively 52.3%,35.2%,75.0%,43.5% and 73.9%,and the incidence of Barrett esophagus was respectively 23.8 %,23.5%, 62.3%,26.1% and 56.5%.Metaplastic columnar epithelium showed a villous structures constituted by goblet cells and columnar cells.EAC occurred in group B,D and F.3 Survival and death About 3hrs after operation the rats got awake,which could only crawl slowly with poor spirit and driftlessness.Theyshowed indifferent response to external stimuli.Rats were fasted for 24 h after operation and were permitted to drink water freely.Spirit, food and water intake returned to normal usually after 3d.They could gradually move freely.6 rats died intraoperatively.14 rats died perioperatively.12 rats died Before 12 weeks.There were a total of 35 deaths with a mortality of 23.3%(35/150). Among these seven was aspiration pneumonia,accounting for 22.8%(8/35), seven was anastomotic stricture, accounting for 20.0%(7/35), four was the accidental anesthesia,accounting for 14.3%(5/35),and six was unexplained, accounting for 17.1%(6/35).Cause of death was mainly anastomotic leakage, pulmonary and abdominal infections, and etc.There were no deaths in group A.Conclusions:1 Barrett’s esophagus in rats can be successfully induced by esophago- jejunostomy anastomosis,esophagoduodenal anastomosis or esophago-gastro- dudenal anastomosis.The addition of iron can signifycantly increase the esophageal injury, and accelerate the occurrence of Barrett’s esophagus.2 Only researchers who have a rich knowledge of anesthesia,anatomy, physiology and a skilled surgical basis can successfully establish a rat model of Barrett’s esophagus and adenocarcinoma. Timely treatment of complica- tions and postoperative care is essential key to reduce mortality. |
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