| Alzheimer’s disease(AD)is a degenerative disease of the central nervous system.The age of onset is mostly elderly,and the course of disease is irreversible.The etiology and pathogenesis of AD are not completely clear,and may be related to a variety of factors,and there are a variety of hypotheses.The incidence of AD is increasing year by year,and patients with AD need long-term drug treatment and care from others.Their cognitive,memory and other advanced activities are gradually declining to varying degrees,which brings a lot of inconvenience to their families and imposes a certain burden on the national economy.One of the hypotheses for AD is synaptic dysfunction.Synapse is an important node of neural network connection.The transmission of information between nerve cells is accomplished through the function of synapses.Synaptic destruction is already present in the early stages of AD.The cholinergic system is a class of nerve cells in which acetylcholine is a neurotransmitter.Acetylcholine is one of the neurotransmitters most closely related to learning and memory.Synaptic destruction results in the failure of the cholinergic system to function properly,which in turn leads to the reduction of acetylcholine release,the formation of alzheimer’s disease,learning and memory disorders and other abilities.Dihuang Yinzi decoction is a commonly used prescription for the treatment of AD in clinical practice,which could tonify the kidney and replenish essence,reduce phlegm and dredge collaterals.For AD patients with cognitive and life ability and other aspects of significant improvement.Its influence on synaptic structure and function and biological mechanism of kidney-tonifying,phlegm-clearing and collaterals-dredging need to be further explored.This study attempts to explore the possible biological mechanism of the effect of on Dihuang Yinzi decoction tonifying kidney and dredging collaterals and its protective effect on synapses and cholinergic system in AD model animals.OBJECTIVETo observe the protective effect of Dihuang Yinzi decoction on synaptic function and cholinergic system in AD model mice.To explore the biological mechanism of Dihuang Yinzi decoction for tonifying kidney and dredging collaterals.METHODSThis experiment adopts the APP/PS1 transgenic mice as animal model of AD,which were randomly divided into model group,Dihuang Yinzi decoction high,medium and low dose group,at the same time in C57BL/6J as blank control group.Choose gastric drug delivery in 150 days in a row,and adopt Morris water maze,Y maze and platform experiments such as behavioral science experiment to observe the learning and memory in mice and the working memory capacity(experiment one);The activity of acetylcholinesterase(AchE)and acetylcholinesterase transferase(ChAT)in brain tissues of mice in each group was determined by spectrophotometry.The expression levels of AchE,ChAT,Syn-1,PSD-95 and α7-nAchR proteins in brain tissues of mice in each group were determined by Western Blot(experiment two).SPSS23.0 statistical software was used to analyze and process the experimental data.RESULTSExperiment one1.Morris water maze experiment:in the positioning navigation experiment,starting from the second day of the experiment,compared with the model group,the incubation period of the high,medium and low dose Dihuang Yinzi decoction group was significantly shortened(P<0.05).No significant difference in average swimming speed(P>0.05).In the space exploration experiment,the target quadrant residence time and relative quadrant residence time of the high,medium and low dose group of Dihuang Yinzi decoction were reduced compared with the model group(P<0.05).The Times of crossing the platform in the high,medium and low dose group of Dihuang Yinzi decoction were less than those in the model group(P<0.05).There was no significant difference in escape latency between groups in the visual platform experiment(P>0.05).2.Y maze experiment:there was no significant difference in the total number of arm intakes of mice in each group(P>0.05).Spontaneous alternation rate of Dihuang Yinzi decoction in high,medium and low dose group was higher than that in model group(P<0.05).3.Platform jumping experiment:compared with the model group,the incubation period of Dihuang Yinzi decoction in the high,medium and low dose groups was prolonged(P<0.05),and the number of errors decreased(P<0.05).Experiment two1.Determination of AchE and ChAT activity:compared with the model group,the AchE activity was significantly reduced in the high,medium and low dose group of Dihuang Yinzi decoction.(P<0.01).The ChAT activity increased(P<0.05).2.Determination of AchE and ChAT protein content:compared with the model group,the AchE protein content was decreased in the high,medium and low dose group of Dihuang Yinzi decoction(P<0.01).ChAT levels increased(P<0.05).3.Determination of Syn-1,PSD-95 and α7-nAchR protein expression:compared with the model group,the content of Syn-1 protein in the high,medium and low dose group of Dihuang Yinzi decoction all increased(P<0.05).The content of PSD-95 protein in the high,medium and low dose group was significantly increased(P<0.01).The protein content of α7-nAchR was increased in high,medium and low dose group(P<0.05).CONCLUSIONDihuang Yinzi decoction can improve the learning and working memory of AD model mice.Dihuang Yinzi decoction can reduce the activity of acetylcholinesterase and down-regulate the protein expression,improve the activity of acetylcholinesterase transferase and up-regulate the protein expression to protect the cholinergic system.The expression of Syn-1,PSD-95,α7-nAchR protein in Dihuang Yinzi decoction can regulate synapse function.The effect of Dihuang Yinzi decoction on tonifying kidney and dredging collaterals may be achieved by improving synapse function and protecting cholinergic system. |
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