Ma Qiming, Gao Jiamin, Xiao Zitian, Yuan Xiaoqi, Wang Yueheng, Tian Lifang, Wang Chuzhuo, Xiang Pengcheng, Zhao Xiuhao, Han Junyi
Objective To establish an improved mouse model of gastroesophageal reflux disease （GERD） by combining partial pyloric and forestomach ligation with postoperative dietary intervention. Methods A total of 48 C57BL/6J mice were randomly assigned to four groups： 2-week sham, 2-week model, 7-week sham, and 7-week model. Model groups underwent partial ligation at the pylorus （pyloric semi-ligation） and forestomach, followed by a high-fat diet and postoperative nutritional gel. Sham groups received laparotomy only and standard chow. Body weight and survival were monitored. At 2 and 7 weeks, esophagi were harvested for hematoxylin-eosin （HE） histology to assess reflux esophagitis, and model induction success was calculated. Inflammatory profiles were evaluated by quantitative real-time PCR （qRT-PCR） and enzyme-linked immunosorbent assay （ELISA）. Statistical analyses were performed in GraphPad Prism. Results Successful model induction rates were 83.3% at 2 weeks and 66.7% at 7 weeks （P<0.05）. Compared with shams, model mice exhibited esophageal wall thickening, basal cell hyperplasia, and inflammatory cell infiltration on HE staining. qRT-PCR and ELISA demonstrated significantly increased expression of M1 macrophage-associated mediators and markers （e.g., interleukin-6], monocyte chemoattractant protein 1, cluster of differentiation 80 [CD80], CD86） and decreased expression of M2-associated mediators and markers （e.g., interleukin-10, CD163, CD206） in model mice （all P<0.05）. Conclusion This combined surgical-dietary approach induces robust reflux esophagitis while maintaining acceptable survival. The model recapitulates key pathological features of human acid-reflux-related GERD, including M1-predominant inflammation, and provides a practical platform for mechanistic studies and preclinical therapeutic evaluation.
