Effect and mechanism of dihydromyricetin on cognitive dysfunction in model rats with Alzheimer's disease / 中华行为医学与脑科学杂志

ABSTRACT

Objective@#To explore the protective effect and mechanism of the dihydromyricetin (DHM) on cognitive dysfunction in Alzheimer’s disease (AD) rat model.@*Methods@#The AD model of rats was established by injecting Aβ1-42 oligomolymer into the hippocampus. According to the random number table, 30 successfully constructed AD model rats were divided into AD group, AD+ DHM1 group and AD+ DHM2 group, with 10 in each group.And the rats in the three groups were intraperitoneally injected with normal saline, 100 mg/kg DHM and 200 mg/kg DHM for 21 days, respectively.Another 10 rats with body mass matching were taken as the control group.Morris water maze was used to evaluate the spatial learning and memory ability of rats in each group, the expression of inflammatory cytokines were detected by Elisa, and the expressions of AMPK and SIRT1 proteins were detected by Western blot.@*Results@#Compared with the control group, the escape incubation period of rats in AD group was prolonged, and the difference was statistically significant (day 5 : (10.36±2.80)s, (22.40±2.98)s; t=-18.63, P<0.05). Compared with AD group, the escape latency of rats in AD+ DHM1 group and AD+ DHM2 group were shortened (day 5: AD+ DHM1 group (15.68±3.06) s, AD+ DHM2 group (18.85±3.22) s; t=10.65, 4.13, both P<0.05). Compared with AD group, rats in AD+ DHM1 group and AD+ DHM2 group had more crossing times ((1.87±0.76), (2.75±0.63) and (3.78±0.71); t=-6.86, -9.83, both P<0.05), and the target quadrant residence time were extended ((17.08±1.99) s, (16.33±4.33) s, (22.59±4.21) s; t= 28.5, 8.63, both P<0.05). Compared with the control group, the levels of IL-1β, IL-6 and TNF-α in the serum and hippocampus of the AD group were significantly increased (serum: t=4.98, 7.87, 5.43, all P<0.05; hippocampus: t=11.13, 30.50, 23.38, all P<0.05). Compared with the AD group, the levels of IL-1β, IL-6 and TNF-α in the serum and hippocampus of the AD+ DHM1 group and the AD+ DHM2 group were significantly decreased, the difference was statistically significant(serum: AD+ DHM1 group t=-4.13, -10.70, -9.22, AD+ DHM2 group t=-1.75, -3.63, -18.75, all P<0.05; hippocampus: AD+ DHM1 group t=-69.13, -15.13, -6.50, AD+ DHM2 group t=-10.25, -39.00, -8.00, all P<0.05). Compared with the control group, the expression of p-AMPK/AMPK protein and SIRT1 protein in the AD group were decreased.The expression of the two proteins in the AD+ DHM1 group and the AD+ DHM2 group were increased, comparing with those of AD group, and the difference was statistically significant(all P<0.05).@*Conclusion@#DHM exerts protective role in AD model rats, which may be related to the activation of AMPK/SIRT1 pathway and the inhibition of inflammatory response.