慢性胃食管反流病大鼠模型制备方法的探讨

Rat chronic gastroesophageal reflux disease model: a study of 3 preparation methods

目的:探讨保留全胃的3种类型慢性胃食管反流病(GERD)动物模型制备方法,以提高模型制备的质量及成功率。方法:雄性SD大鼠,随机分为假手术(SO)对照组(n=20)、十二指肠胃食管反流(DGER)组(n=47,食管胃十二指肠吻合术)、单纯胃食管反流(GER)组(n=20,幽门部分缝扎+贲门肌切开术改行胃底食管吻合术)、十二指肠食管反流(DER)组(n=21,空肠食管吻合术改行胆总管开口远侧十二指肠与食管吻合术),分别制备保留全胃的3种类型GERD动物模型。术后对动物持续喂养观察及测量体质量,并对非预期死亡动物随即进行尸体解剖;存活动物分批于术后1、2、3、4个月处死进行食管病理分析。结果:麻醉意外死亡3只。术后非预期死亡26只(24.1%),其中DGER组死亡18只(38.3%),GER组1只(5%),DER组死亡7只(33.3%)。SO组中动物未见死亡。尸解分析死亡原因有梗阻、感染、窒息、出血、吻合口瘘和穿孔等。各模型组存活动物均可见不同程度病变形成,且术后生存质量良好。结论:本研究所采用的保留全胃的3种类型慢性GERD动物模型制备方法,模型质量及病变形成率高,但术后动物死亡率亦较高。要制备符合研究需要的慢性GERD动物模型,不但要选择合理的术式以保证模型质量,还要采取一定措施预防术后并发症,降低非预期死亡率,以提高模型制备成功率。

Objective： To introduce 3 methods for preparation of stomach-conserving gastroesophageal reflux disease （GERD）model in rats, so as to improve the quality and successful rate of model preparation. Methods： Male Sprague-Dawley rats were divided into sham-operated（SO） group （n= 20） and 3 stomach-conserving reflex model groups： d uodenogastroesophageal reflux （DGER） group （n= 47, esophagogastroduodenal anastomosis）, gastroesophageal reflux（GER） group（n= 20, partial pyloric ligation ＋ cardiomyotomy followed by gastric fundus-esophagus anastomosis） and duodenoesophageal reflux （DER） group （n= 21, jejuno-esophageal anastomosis followed by duodeno-esophageal anastomosis）. Rats were observed closely after operation and their body weights were monitored. The rats that died unexpectedly were autopsied immediately and the surviving rats were sacrificed to observe the esophageal pathological changes at 1, 2, 3, and 4 months after operation. Results： Three rats died due to anesthetic accidents;26 （24. 1% ） died unexpectedly after operation, 18（38.3%）in DGER group, 1 （5%） in GER group, and 7（33.3%）in DER group; no rat died in SO group. Necropsy showed that the death cause of rats included obstruction, infection, asphyxia, hemorrhage, anastomosis leakage and perforation, etc. Esophageal pathological changes were noticed in all rats of 3 model groups; the life quality of surviving rats was good. Conclusion： The 3 methods for establishing rat stomach-conserving GERD model can produce high quality model and high rate of pathological changes, but with high post-operation mortality. In addition to rational operative methods, avoiding post-operation complications and unexpected death are also very important for successful GERD model preparation.