Objective To investigate the possible molecular mechanism of mitochondrial ATP-sensitive potassium(KATP) channel opener diazoxide in preventing cytotoxicity of Aβ1-42.Methods Primary neurons were cultured and evaluated by immunocytochemistry.Cells were randomly divided into 5 groups: the control group,the Aβ1-42 group,the diazoxide + Aβ1-42 group,the diazoxide group and the Aβ42-1 group.After treatment for 24 h or 72 h,subunits of KATP(Kir6.1,Kir6.2,SUR1 and SUR2) were detected by double immunofluorescence and immunoblotting.Results ① Being treated with Aβ1-42(2 μmol / L) for 24 h,expressions of Kir6.1 and SUR2 were significantly up-regulated,and the changes could be completely reversed by pretreatment with diazoxide(1mmol / L) for 1 h(P 0.05).② There were significant increases in all KATP subunit expression levels after exposure to Aβ1-42 for 72 h,and up-regulation of Kir6.1,Kir6.2 and SUR2 except SUR1 could be partly reversed by pretreatment with diazoxide(1 mmol / L) for 1 h(P 0.05).Conclusion Diazoxide could reverse enhanced expressions of KATP subunits in neurons caused by exposure to Aβ1-42,which may explain,in part,the effect of diazoxide on resistance to the toxicity of Aβ1-42.