The protective effect of rapamycin on beta-amyloid protein 25-35-induced PC12 cells death / 医学研究生学报

ABSTRACT

Objective Rapamycin can improve characteristic pathology of AD by improving the level of autophagy.But, its internal mechanism still needs further study.This study was aimed to observe the protective effect of Rapamycin (RAPA) on the injury of rat pheochromocytoma (PC12) cells induced by β-amyloid protein25-35 (Aβ25-35).Methods PC12 cells in the logarithmic phase were randomly divided into 5 groups control group(similar free-serum DMEM), model group, 10μmol/L RAPA treated group, 40μmol/L RAPA treated group and 160μmol/L RAPA treated group(add 10μmol/L, 40μmol/L RAPA, 160μmol/L respectively).Except the control group, each group was cultured with 20μmol/L Aβ25-35 to established the cell injury model.Results ①Compared with the survival rate of cells[(51.47±2.59)%] and the apoptosis rate of cells[(52.22±2.33)%] of the model group,the survival rate of cells in 10、40、160μmol/L RAPA treated groups and control group[(54.64±2.42)%, (64.79±2.91)% ,(56.50±2.55)% and (99.98±0.73)%] significantly increased, but the apoptosis rate of cells [(45.33±2.83)%, (36.89±2.85)%, (48.00±2.83)% and (3.33±2.45)%] significantly decreased(All P<0.05).②In model group,the expressions of p-PKB is 0.33±0.01, p-mTOR is 1.97±0.05, p-tau is 2.09±0.19.Compared with model group, in 10、40、160μmol/L RAPA treated groups and control group,these expressions of p-PKB (0.37±0.01, 0.42±0.01, 0.40±0.01 and 0.44±0.02) were significantly increased, however p-mTOR (1.64±0.05, 0.66±0.04, 0.35±0.01 and 0.62±0.01) and p-tau (2.02±0.15, 1.79±0.05, 1.86±0.06 and1.53±0.04) were decreased(All, P<0.05).ConclusionRAPA can increase Aβ25-35-induced PC12 cells viability, decrease cells apoptosis rates, and have a protective effect on Aβ25-35-induced PC12 cells death.The mechanism of its protective effect may be related to the inhibition of mTOR regulating PI3K/PKB/mTOR signal transduction pathway by negative feedback and the reduction of tau protein hyperphosphorylation.