Abstract:

To investigate the effects of diazoxide (ATPsensitive potassium channel opener) and cyclosporine A and their combination on apoptosis induced by betaAmyloid protein (Aβ142) on cultured primitive rat basal forebrain cholinergic neurons. MethodsThe cell apoptosis model was induced by Aβ142(2?μmmol/L), and then 500?μmol/L diazoxide, 20?μmol/L cyclosporine A and their combination were used to interfere with it. Cell morphology was observed by an inverted microscope,changes of cell apoptosis were determined by MTT, and expressions of target proteins (bcl2, bax, cytochrome C, caspasce3 and Cleaved Caspase3) were determined by Western blot when the neurons were interfered with by the drugs for different times (24, 72?h). Results ① Being exposed to Aβ142 for 72?h, cell activity remarkably decreased(P＜0.001), expression of Bcl2 decreased (P＜0.01) and expressions of cytochrome C, caspasce3 and Cleaved Caspase3 increased(P＜0.01, P＜0.001， P＜0.01). Expression of Bax had no change but the value of Bcl2/Bax decreased(P＜0.01). ② Expression of Bcl2 increased when the cell apoptosis model was exposed to diazoxide, cyclosporine A and their combination for 24?h（P＜0.05， P＜0.01，　P＜0.01). When the cell apoptosis model was exposed to diazoxide, cyclosporine A and their combination for 72?h, expression of Bcl2 obviously increased (P＜0.05, P＜0.01, P＜0.001), expressions of Cytochrome C, Caspasce3 and Cleaved Caspase3 decreased(P＜0.05, P＜0.01, P＜0.001), and cell activity increased(P＜0.01, P＜0.001). ConclusionBeing exposed to Aβ142 for 72?h，　neuron apoptosis occurs. Diazoxide and cyclosporine A and their combination could protect neurons from apoptosis induced by Aβ142.

Key words: Amyloid betaprotein, Diazoxide, Cyclosporine, Cholinergic neuron, ATPsensitive potassium channel, Rats,Wistar