Published online Sep 15, 2024. doi: 10.4239/wjd.v15.i9.1962
Revised: July 17, 2024
Accepted: August 12, 2024
Published online: September 15, 2024
Processing time: 83 Days and 3.9 Hours
Diabetes is often associated with gastrointestinal dysfunctions, which can lead to hypoglycemia. Dexmedetomidine (DEX) is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function.
To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction.
Sedation/anesthesia scores and vital signs of streptozotocin (STZ)-induced diabetic mice under DEX sedation were observed. Diabetic mice were divided into saline and DEX groups. After injecting sedatives intraperitoneally, tight junctions (TJs) and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function. The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion. In vitro, high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ inter-vention. Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions.
MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice, with the DEX group displaying decreased MMP23B levels. Diabetes-mediated TJ dis-ruption, increased intestinal mucosal permeability, and systemic inflammation in wild-type mice might be reversed by DEX. In Caco-2 cells, MMP23B was associated with increased reactive oxygen species accumulation, mitochondrial membrane potential depolarization, and TJ disruption.
DEX reduces MMP23B, which may potentially contribute to STZ-induced intestinal barrier dysfunction, affecting TJ modification through mitochondrial dysfunction.
Core Tip: This study investigates the protective role of dexmedetomidine (DEX) in diabetic intestinal injury through the MMP23B pathway. The findings reveal that DEX acts as a sedative and enhances intestinal barrier function by promoting M2 macrophage polarization and reducing mitochondrial dysfunction. Streptozotocin-induced diabetic mice and Caco-2 cell models provide robust evidence of the potential therapeutic benefits of DEX, offering insights into its dual functionality in managing sedation and intestinal healing under diabetic conditions. This research can pave the way for the development of new treatment strategies targeting intestinal complications in diabetic patients.