| Objective:Alzheimer's disease(AD)is a latent neurodegenerative disease.Patients are characterized by declining memory in recent years,accompanied by behavioral disorders and cognitive disorders.They may also be characterized by mental disorders lastly.Currently,there is no effective drug for the treatment of AD,so it is an urgent problem to develop effective drugs for the treatment of AD.Berberine(BBR)is a kind of natural alkaloid extracted from berberine and it has many pharmacological effects,including anti-inflammatory,anti-tumor,anti-viral,anti-bacterial and lipid-lowering etc.Recent experiments have shown that berberine can serve as one of the drug targets for the treatment of AD.Therefore,the new three-transgenic(3×Tg)mice were used as the animal model of AD.The 8-month aged 3×TgAD mice were selected to study the proective effect of berberine on AD and its mechanism.Method:Water maze was used to examine the location memory and navigation of AD mice at 4,6,and 8-month-old.Meanwhile,Immunohistochemistry was used to find the expression of A?in the 4,6,8-month-old AD mice.WB was used to know the level of APP and A? in the4,6,8-month-old AD.Based on the above results,we selected 8-month-old transgenic mice for the treatment by BBR.8-month-old transgenic mice were taken the 50mg·kg-1·d-1 concentration of BBR by intragastric administration for 12 weeks.At the end of the administration,Morris water maze was used to discover the spatial memory and exploration ability from mice.HE staining was used to detect the changes of nucleus and cytoplasm in neurons of mice.The expression levels of related phosphorylated proteins A?,Tau-5,Tau-ps404,Tau-ps396 and Tau-ps231 were detected by WB respectively;HE,immunofluorescence,immunohistochemistry and are usde to discover related indicators.The oxidative stress of SOD and the expression of Bcl-2 and Bax were detected by related kit.Results:With the increasing the age of 3×Tg AD mice,their memory and learning ability decreased gradually().The neurons in the hippocampus of AD mice were reduced.The number of A?proteins in the brain increased,the same to the level of phosphorylation of Tau protein.The results of immunohistochemistry showed that the expression of A? inhippocampus of 4-month-old 3×Tg AD mice was increased compared with that of4-month-old WT mice,and the expression of A ? deposition in 3 × Tg AD mice increased significantly in 6-8 months(p <0.01).WB showed that the expression levels of A?,APP and Tau5 in hippocampus of 3×Tg AD mice were significantly higher than those in wild type mice(p <0.05).After 8 months of age 3×Tg AD mice were treated with BBR,the preemptive time of mice was significantly decreased(p<0.05).The expression level of A? and Tau protein in hippocampus was significantly lower than that in control group(p <0.05),and the expression level of Tau-ps396 and Tau-pS231 was significantly decreased(p <0.01).The levels of SOD and glutathione in brain of berberine group were significantly increased(p <0.05).The expression of Bcl-2 in berberine was increased and the expression of pro-apoptotic factor Bax was decreased(p <0.05).Conclusion: With the increase of age in 3×Tg AD mice,their performance of the learning and memory decreased,the number of nerve cells in the hippocampus decreased,the accumulation of A? in the brain increased,Tau protein and related sites increased phosphorylation level,so the three transgenic AD Mice can be a good simulation of AD related pathological features and course of progress.The experimental results show that 8 months of age cloud be an important time for pathological changes in 3×Tg AD mice.In those 3-transgenic AD mice,the8-month-old may be a critical moment of the AD pathological progression.Berberine can ameliorate the learning and memory ability of 8-month-old AD mice,inhibit the deposition of A? in the brain and the level of Tau proteinand its hyperphosphorylation,inhibit the apoptosis level of Bax,increase the protection of apoptosisi Bcl-2,decrease the inflammatory response in brain,decrease oxidative stress reaction in brain.It testied that berberine has great potential in the therapy of AD,and our study also has certain practical significance for the research of AD. |
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