Effect of matrine on oxidative damage and apoptosis of PC12 cells via AMPE/SIRT1 pathway in Alzheimer disease induced by Aβ25-35
Objective To investigate the effect of matrine on apoptosis and oxidative damage of PC12 cells induced byβ-amyloid protein(Aβ)25-35 in Alzheimer disease and to analyze the mechanism of its interaction with the AMP-activated protein kinase(AMPK)/silenced information regulator(SIRT1)pathway.Methods The effect of matrine on the growth of PC12 cells was determined using MTT.Matrine concentrations of 0.5,1.0,and 1.5 mmol/L were selected for the experiment.PC12 cells were divided into the Con group(blank culture cells),the Aβ25-35 group(20 μmol/L Aβ25-35 treated cells),the Aβ25-35+Matrine-L group,the Aβ25-35+Matrine-M group,and the Aβ25-35+Matrine-H group(20μmol/L Aβ25-35 were treated with 0.5 mmol/L,1.0 mmol/L,and 2.0 mmol/L matrine).Cell proliferation was detected using MTT.The detection of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)using enzyme-linked immunosorbent assay,expression of B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved caspase-3 containing cysteine,and AMPK/SIRT1 pathway-associated proteins were detected using Western blotting.Results Compared to the Con group,OD value,Bcl-2 protein expression,SOD,and GSH-Px activity decreased at 24 h and 48 h;the apoptosis rate,Bax,cleaved caspase-3 protein expression,ROS content,IL-6,IL-1β,and TNF-α expression increased,and P-AMPK and SIRT1 protein expression were up-regulated in the Aβ25-35 group(all P<0.05).Compared to the Aβ25-35 group,OD value,Bcl-2 protein expression,SOD,and GSH-Px activities in the Aβ25-35+Matrine-L group,the Aβ25-35+Matrine-M group,and the Aβ25-35+Matrine-H group increased at 24 h and 48 h.Apoptosis rate,Bax,cleaved caspase-3 protein expression,and ROS content decreased.IL-6,IL-1β,and TNF-αexpression decreased,and p-AMPK,and SIRT1 protein expression were down-regulated(all P<0.05).Conclusion Matrine may reduce the apoptosis and oxidative damage of PC12 cells induced by Aβ25-35 by inhibiting the AMPK/SIRT1 pathway.