关键词: 淀粉样β蛋白；细胞毒素类；钾通道，电压门控；二氮嗪

Abstract:

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 24h or 72h, subunits of KATP(Kir6.1, Kir6.2, SUR1 and SUR2)were detected by double immunofluorescence and immunoblotting. Results   ① Being treated with Aβ1-42(2μmol/L) for 24h， expressions of Kir6.1 and SUR2 were significantly up-regulated，and the changes could be completely reversed by pretreatment with diazoxide(1mmol/L)for 1h(P<0.05). ② There were significant increases in all KATP subunit expression levels after exposure to Aβ1-42 for 72h， and up-regulation of Kir6.1, Kir6.2 and SUR2 except SUR1 could be partly reversed by pretreatment with diazoxide(1mmol/L) for 1h(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.

Key words:  Amyloid betaprotein； Cytotoxins； Potassium channels， voltagegated； Diazoxide