Effect of Rhizoma-Anemarrhenae-Cortex Phellodendri on abnormal autophagy of hippocampal neurons in D-gal cognitive impairment model mice
Objective:To explore the mechanism of Rhizoma Anemarrhenae-Cortex Phellodendri(AP)in ameliorating cogni-tive dysfunction in D-galactose(D-gal)model mice by observing the expression level of autophagy-related proteins in the hippo-campus.Methods:Seventy-five mice were randomly divided into blank group,model group,piracetam group,AP group and au-tophagy inducer everolimus(RAD001)group.Except for the blank group,all the other groups were injected with 0.125 g∙kg-1∙d-1 D-gal intraperitoneally to replicate the cognitive impairment model.The cognitive dysfunction of mice was tested by water maze ex-periment.The neuron status and Nissl bodies of hippocampus in each group were observed by HE staining and Nissl corpuscle number.The expression of LC3 and P62 positive cells in hippocampus was detected by immunohistochemistry.The relative ex-pression levels of autophagy-related proteins such as ULK1,LC3,Beclin-1 and P62 were detected by Western Blot.The genes such as ULK1,Beclin-1 and P62 were detected by real-time fluorescence quantitative PCR.Results:Compared with the blank group,the learning memory ability of mice in the model group was significantly reduced,and neurons and Nissl bodies in hippo-campal CA1 area were seriously lost and arranged in disorder.The expression of ULK1,LC3,Beclin-1 protein and gene in hippo-campus increased(P<0.01,P<0.05),while the expression of P62 protein and gene decreased(P<0.01).Compared with the model group,the learning memory ability of mice in the piracetam and AP groups was significantly improved,and the loss of neu-rons and Nissl bodies decreased.The expression of ULK1,LC3,Beclin-1 protein and gene in hippocampus decreased(P<0.01),while the expression of P62 protein and gene increased(P<0.01).RAD001 group showed that AP could partially reverse the au-tophagy of cells after administration.Conclusion:AP can improve the cognitive dysfunction of D-gal model mice,and its mecha-nism may be achieved by inhibiting autophagy of hippocampal cells.
Rhizoma Anemarrhenae-Cortex Phellodendri Pair of drugs(AP)D-gal modelCognitive dysfunctionAutoph-agy
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