| Objective: To explore the therapeutic effects of Panax Notoginseng Saponins on Alzheimer’s disease through PI3K/Akt and PLCγ1/PKC oxidative stress signaling pathways.Methods: Three-month-old male senescence accelerated prone mouse(SAMP8)were used as experimental group and randomly divided into four groups with 15 mice in each group: model group,low-dose PNS group(100mg/kg),high-dose PNS group(200mg/kg)and Huperzine-A group(0.3mg/kg),another fifteen healthy male SAMR1 were used as the normal control group.All the mice were fed adaptively for one week,the PNS groups and Huperzine-A group were treated with the designed drugs per day by intragastric administration for 8 consecutive weeks,and the same volume of normal saline was given to the control group and model group.Morris water maze test was used to assess the change of learning and memory abilities of each group mice;HE staining was applied to obeserve the pathological change in hippocamus of all the experimental mice;PKC kit was used to detecte the activity of PKC in the brains of SAMP8 mice;the m RNA expression levels of PI3 K,Akt,PLCγ1 and PKC were detected with Real-time Quantitative PCR(RT-q PCR) technique;the expression of PI3 K,p-Akt,Akt,p-PLCγ1 and PLCγ1 proteins in the brains of mice were observed by immunohistochemical method and Western blot.Results: 1.Morris water maze test showed that:(1)place navigation: Compared with the control group,the average escape latency was obviously longer than that in the model group(P<0.01)and the percentage of time spent in target quadrant of model group significantly decreased(P<0.01);the escape latency of the PNS groups were decreased compared to model group(P<0.01)and the percentage of time spent in target quadrant were increased with significant difference(P<0.01).(2)spatial probe: As compared with the control group,the percentage of time spent in original target quadrant of model group decreased(P<0.05);while the PNS groups were significantly increased compared to model group(P<0.05),these suggested that PNS could impair the learning and memory abilities of SAMP8 mice.2.HE staining result showed that: The numbers of neuron in hippocamus of model group drastically reduced as compared to control group;Compared with the model group,the hippocampus neuron structural in the brains of SAMP8 mice in the PNS groups had improved,the cells were well-distributed and ordered,the number of neurons and the cone cells were increased but gliocyte proliferation was decreased.3.PKC kit result showed that: Compared with model group,the PKC activity in the brains of low-dose PNS group and high-dose PNS group were significantly increased(P<0.01).4.RT-q PCR result showed that: Compared with the model group,the m RNA expression of PI3 K in the brains of low-dose PNS group were significantly increased(P<0.05),the gene expression of Akt,PLCγ1 and PKC m RNA in the low-dose PNS group were enhanced but not statistically significant(P>0.05),while PI3 K,Akt,PLCγ1 and PKC m RNA expression in the brains of high-dose PNS group were significant increased(P<0.05 or P<0.01).5.Immunohistochemical result showed that: Compared with the control group,the percentage of positive cells number and total cells within each vision of PI3 K,p-Akt,Akt,p-PLCγ1 and PLCγ1 proteins in hippocampus of model group were all significantly decreased(P<0.05 or P<0.01);however,the percentage of positive cells number of these proteins in the PNS groups were all higher with significant difference than that in the model group(P<0.05 or P<0.01).6.Western blot result showed that: Compared with the control group,protein expression levels of Akt and PLCγ1 were decreased in the model group but there were no significant difference(P>0.05),while the PI3 K,p-Akt and p-PLCγ1 proteins expression were significantly decreased(P<0.05 or P<0.01);the levels of these proteins expression of PNS groups in the brains of SAMP8 were all increased compared to model group,one of the PI3 K,p-Akt and p-PLCγ1 proteins expression were significantly increased(P<0.05 or P<0.01).Conclusion:1.PNS could improve the learning and memory abilities of SAMP8 mice.2.PNS through activating PI3K/Akt and PLCγ1/PKC signaling pathways so that it could inhibit the brains impairment which caused by oxidative stress of Alzheimer’s disease. |
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