Objective:To investigate the effect of catalpol-tetramethylpyrazine(CT) prescription on Alzheimer's disease(AD).Methods:Wild-type C57BL/6J mice were used as Control group,and the mice double-transfused with powder precursor protein/presenilin 1 were randomly divided into Model group,low-dose CT prescription(CT-L) group and high-dose CT prescription(CT-H) group according to random number table method,with 6 mice in each group.The CT-L group and the CT-H group were given 50 and 100 mg/kg intragastric treatment of catalol-ligustrazine,respectively.Both Control group and Model group were given equal volume of normal saline intragastric administration.Once a day for 8 weeks.The effect of tetramethylpyrazine on the learning and memory ability of AD mice were explored by water maze experiment,and the expression of growth-related protein 43 ( GAP-43) in hippocampus was detected by immunohistochemistry.HT-22 cells of hippocampal neurons were divided into Control group,Model group,low-dose CT treatment(CT-L) group,high-dose CT treatment (CT-H) group,STAT3 knockout+CT treatment(CT+siSTAT3) group.The AD model in vitro was constructed by Aβ1-42,and the STAT3-silenced neuron model was constructed by transfection siSTAT3,and then cultured for 24 h with high and low doses of CT prescription.Cell activity assay(CCK-8) measured cell viability.The expression levels of Cyclin D1,Ki-67,B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax),NF200,GAP-43,STAT3 and phosphorylated STAT3(p-STAT3) protein were detected by Western Blot.Cell proliferation was detected by Brdu.Apoptosis was detected by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL).Results:CT prescription significantly shortened the escape latency of APP/PS1 double-transfected mice,increased the targed quadrant residence time and number of target quadrant stays,and up-regulated the expression of GAP-43 in hippocampus,and the effect of high dose of CT prescription was more significant(P<0.05 or P<0.01).CT prescription restored the activity and proliferation ability of AD model cells,up-regulated the expression of Cyclin D1,Ki-67,NF200,GAP-43,and STAT3 proteins,down-regulated the expression of apoptosis-related protein Bax and restored the level of anti-apoptotic Bcl-2 protein,the effect of high dose tetramethylpyrazine formula was more significant(P<0.05 or P<0.01).However,silenced STAT3 reversed the promoting effect of CT prescription on the proliferation of AD neurons and the expression of NF200 and GAP-43 proteins,and blocked the anti-apoptosis effect of CT prescription on AD neurons(P<0.05 or P<0.01).Conclusion:CT prescription can significantly improve the cognitive and memory ability of AD model mice,and the effects are dose-dependent.The mechanism of action may be related to promoting the proliferation of neuron cells,reducing apoptosis,regulating the expression of STAT3 and thus promoting the plasticity of neurons.
Alzheimer's diseasecatalpol-tetramethylpyrazine prescriptionsignal transduction and transcriptional activation protein 3axonal plasticityexperimental study
维普
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