Liang Jin ¹ Yuan Zhao ^2* Xiaojing Qian ² Lingyun Pan ² Long Chen ² Jingwen Feng ^2* Xinhua Liu ^2* Xiaotong Lu ^1*

• ¹ Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
• ² Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Municipality, China

Background: Postoperative Intestinal Adhesions (PIAs) remain a significant complication of abdominal surgery that can cause pain, infertility, and a potentially lethal bowel obstruction. Kangnian (KN) decoction, a Traditional Chinese Medicine prescription, has been shown to be effective in treating PIAs. Nevertheless, its underlying mechanisms remain unclear. Objective: This study aims to explore the therapeutic effects of KN decoction in a PIA rat model, as well as its potential mechanisms via metabolomics and proteomics analyses. Materials and methods: 60 rats were randomly assigned to six groups: Normal Control (NC), PIA model, Dexamethasone, KN-Low, KN-Medium, and KN-High. The PIA model was created by abdominal surgery under anesthesia. Pathological damage was evaluated through H&E staining and adhesion grading of affected tissues. The levels of serum cytokines (IL-1β, IL-6, TNF-α, and TGF-1), Connective Tissue Growth Factor (CTGF), and Motilin (MTL) in adherent intestinal tissues were detected using ELISA kits. Untargeted metabolomics was used to investigate potential metabolic pathways of the KN decoction intervention in intestinal adhesions and to screen for differential biomarkers. The label-free quantitative proteomics technique was employed to detect Differentially Expressed Proteins and for biological function and pathway enrichment analyses. Results: In PIA rats, KN decoction significantly improved the pathological injury associated with intestinal adhesions and effectively regulated the blood inflammation indicators. Furthermore, KN presented a favorable anti-fibrotic and protective effect against abdominal adhesions, effectively modifying gastrointestinal motility disorders in PIA rats. We identified 58 variables as potential biomarkers and discovered seven main pathological pathways that may be associated with PIAs. Proteomics analysis revealed 75 DEPs that were primarily involved in Valine, leucine, and isoleucine degradation, the MAPK signaling pathway, and retrograde endocannabinoid signaling. Conclusion: This study proved that KN reduces intestinal mucosal injury, downregulates inflammatory factors, and alleviates intestinal adhesions, thus protecting the intestinal barrier function in PIA rats. The combination of proteomics and metabolomics provided a feasible approach for unraveling the therapeutic mechanism of KN decoction in PIAs.