Yiqi Daozhi Formula Reduces the M1 Polarization of Macrophages in Mice With Postoperative Ileus Through Mediating Glycolysis Metabolism.

Abstract

BACKGROUND: Postoperative ileus (POI) represents a disorder of gastrointestinal function following surgical procedures, characterized by a multifaceted etiology. There is an urgent clinical need to search for treatment regimens that improve the therapeutic effect for POI. Current research indicates that Traditional Chinese Medicine (TCM) demonstrates significant efficacy in treating POI. Our research was conducted to delve into the precise therapeutic action of Yiqi Daozhi Formula (YQDZF) in the treatment of POI. METHODS: In our study, H&E staining and carmine detection were employed to assess the gastrointestinal functionality in the POI mouse model. ELISA was used to detect levels of MPO, lactic acid, inflammatory factors, and glycolysis. Flow cytometry and qRT-PCR were employed to examine the levels and expression of macrophage phenotypic markers. Western blotting was used to detect the expression of glycolysis- and AKT/NF-kB/HIF-1α signaling pathway-related proteins. Cycloheximide method and MG-132 method were used to detect the stability of AKT protein. RESULTS: After making the comparative analysis with the Control group, the POI group mice exhibited pronounced gastrointestinal dysfunction, which was mitigated by treatment with YQDZF. In vivo experiments confirmed that YQDZF treatment markedly decreased M1 macrophage polarization and inhibited the glycolytic pathway. Cellular experiments demonstrated that this therapeutic approach was related to the AKT/NF-kB/HIF-1α signaling pathway in macrophages. CONCLUSIONS: YQDZF inhibits the AKT/NF-kB/HIF-1α pathway, thereby mediating the M1 polarization of macrophages and the glycolytic metabolism to effectively alleviate the progression of POI.