Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway  

作　　者：Man Lu Xiao-Wen Guo Fang-Fang Zhang Dan-Hong Wu Di Xie Feng-Qin Luo 

机构地区：[1]Department of Anesthesiology,The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine),Hangzhou 310006,Zhejiang Province,China [2]Department of Emergency,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China

出　　处：《World Journal of Diabetes》2024年第9期1962-1978,共17页世界糖尿病杂志（英文版）（电子版）

摘　　要：BACKGROUND 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.AIM To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction.METHODS 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 intervention.Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions.RESULTS 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 disruption,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.CONCLUSION DEX reduces MMP23B,which may potentially contribute to STZ-induced intestinal barrier dysfunction,affecting TJ modification through mitochondrial dysfunction.

关 键 词：DIABETES DEXMEDETOMIDINE Intestinal barrier Piezo1 Tight junctions 

分 类 号：R587.1[医药卫生—内分泌]