Abstract
Gastric ulcer (GU) is a prevalent gastrointestinal disorder characterized by distinct symptoms and frequent recurrence. Despite diverse etiologies and precipitating factors, the impact of environmental and dietary factors on GU remains underexplored. With the intensification of global climate change, the health risks associated with heat stress in hot-humid environments are becoming increasingly severe, especially when coupled with unhealthy dietary habits. Emerging evidence suggests that the hot-humid climate prevalent in hygrothermal regions may aggravate GU-related complications. Therefore, this study investigates the effects of a hygrothermal environment and a high-sugar, high-fat diet on GU development and explores the underlying mechanisms. A rat model (GU-HH) was successfully established by exposing rats to a hot-humid environment and feeding them a high-sugar, high-fat diet for 56 days, followed by 56% ethanol/H₂O administration for 7 days. Throughout the experiment, the normal control (NC) and GU groups were housed under standard conditions and received a regular diet. Concurrently with the GU-HH group, the GU group also received intragastric administration of 56% ethanol/H₂O. The model rats were evaluated through physiological data collection, histopathological examination, complete blood count, inflammatory cytokine measurement, blood viscosity assessment, and biochemical evaluations. Label-free proteomic analysis was employed to detect proteins with differential expression. The GU-HH model exhibited severe gastric tissue damage, pronounced inflammation, disrupted glucolipid metabolism, and compromised hepatorenal function compared to both the NC and GU groups. Proteomic analysis revealed upregulation of the complement and coagulation cascade pathways and downregulation of the oxidative phosphorylation pathway. Four key differential proteins were validated. This study presents the first comprehensive analysis of the combined effects of a hot-humid environment and a high-sugar, high-fat diet on GU development, with the identification and validation of four potential biomarkers. The improved GU-HH model offers a controlled research environment for developing innovative Chinese herbal medicine and highlights the importance of considering living conditions and diet in GU treatment.