Dexmedetomidine Protects Intestinal Mucosal Barrier via Activating theα7-nAChR-GDNF in Enteric Glial CellsOA

Objective:Intestinal barrier disruption is a critical event in sepsis and ischemia-reperfusion(I/R)injury.Enteric glial cells(EGCs)maintain barrier integrity by secreting glial cell line-derived neurotrophic factor(GDNF).This study aimed to determine whether Dexmedetomidine(Dex)protects the intestinal barrier viaα7-nicotinic acetylcholine receptor(α7-nAChR)signaling in EGCs.Methods:An in vitro EGC-intestinal epithelial cell(IEC)co-culture system and amurine intestinal I/Rmodel were established.EGCs were selectively ablated in vivo using benzalkonium chloride(BAC).Barrier integrity was evaluated by transmembrane electrical resistance(TEER)and plasma FITC-dextran permeability.Enzyme-Linked Immunosorbent Assay(ELISA)and Western blotting quantified levels of GDNF and Occludin.Theα7-nAChR antagonist methyllycaconitine(MLA)was applied for mechanistic validation.Results:In vitro,Dex(40-100μm)dose-dependently increased GDNF expression in EGCs(p<0.05)and enhanced IEC TEER.These protective effects were abolished by MLApre-treatment(p<0.05).In vivo,Dex significantly reduced I/R-induced mucosal injury and decreased plasma FITC-dextran concentrations compared to the untreated I/R group(0.30±0.01 vs.0.43±0.02 mg/mL,p<0.05).Notably,in EGC-ablated mice,Dex failed to restore Occludin levels or reduce permeability(p>0.05),confirming EGC-dependence.Conclusion:Dexmedetomidine protects the intestinal mucosal barrier via an EGC-dependent mechanism involvingα7-nAChR activation and GDNF-mediated tight junction reinforcement.These findings highlight EGCs as key effectors of Dex-induced intestinal protection and potential therapeutic targets for barrier dysfunction in critical illness.