Clinical Observation And Experimental Study Of Alzheimer's Disease Treated By Huatuo Zaizao Pills

Background:Alzheimer's disease(AD)is a chronic and progressive central nervous system degenerative disease,which mainly manifested as memory loss,language and behavioral disorders,accompanied with personality changes.Its pathological mechanism is closely related to ?-amyloid induced chronic neuroinflammation and synaptic dysfunction.Huatuo Zaizao Pills is one of the"state-level confidential prescriptions" in China with complex ingredients including many natural botanicals such as Angelica sinensis,Rhizoma Chuanxiong,Safflower,Borneol,Radix Paeoniae Alba,Schisandra chinensis,etc.It has the functions of promoting blood circulation to eliminate blood stasis,Gas analgesic effect.It was widely used in the treatment and prevention of heart,cerebrovascular disease,vascular dementia.Now,there are some reports about AD patients with HT,but the specific mechanism is unknown,there were not have reports about the improvement of dementia model action cognitive impairment.Aims:(1)This study is to observe the clinical effect of HT on the changes of dementia scale and TCM syndromes in patients with AD;(2)To clarify the effect of HT on improving the behavior of APP/PS1 transgenic mice;(3)To investigate the effect of HT on the cognitive function of APP/PS1 transgenic mice and the underlying mechanism.Methods:(1)Part one:30 patients were randomly divided into observation group and western medicine control group,the observation group was treated with Huatuo Zaizao pills combined with memantine,western medicine control group were given memantine.The two groups were given AD education and treated for two months.The clinical efficacy of Huatuo Zaizao Pill was evaluated according to the Alzheimer's Disease Rating Scale(ADAS-cog),TCM Syndrome Integral Scale and ADL's social activity ability.(2)Part two:We used the APP/PS1 transgenic mouse to test the pharmacological effects of HT.Open Field,Novel Object Recognition and Morris Water Maze were manipulated to explore whether HT has effects in improving cognitive dysfunction of APP/PS1 mice.Neurophysiological analysis was used to assess the synaptic function in APP/PS1 mice.Golgi staining was used to detect dendritic spine in APP/PS1 mice.The morphological changes of hippocampus and cortex in hippocampus of APP/PS1 mice were observed by HE staining.Immunostaining was used to evaluate A? plaque in the brain of APP/PS1 mice.Western blot was used to access the protein levels of PS1,ADAM 10,BACE1,SYN,APP,IDE and PSD95 in hippocampus of APP/PS 1 mice.Results(1)Part one:AD patients have similar proportions of gender,the average age was 68.2 years;the level of education is mainly secondary school and there are few people who have received higher education.There are not many.These pepeople are mostly with underlying diseases,such as hypertension,coronary heart disease,hyperlipidemia,diabetes.Some men have smoking and drinking habits.They don't have similar Genetic disease.The study found that Huatuo Zaizao Pills can significantly improve the AD patients with TCM syndrome,such as phlegm and vomiting,limb drowsiness,dull lookd.ADAS-cog scores were compared between groups after treatment,the observation group have no significant changes in the love of tears,hallucinations,test cooperation,attention,verbal;the remaining items were statistically significant,P<0.05.Compared with the control group,there was no significant improvement in 8 items of love,tears,delusions,hallucinations,drawing,attention,test cooperation,verbal language and named objects in the control group,P>0.05.The two groups before and after treatment were compared between the two groups after treatment,the difference was significant,P<0.05.Before and after treatment,the scores of MMSE in observation group changed significantly,MMSE score increased,P<0.05,there was a significant statistical difference;MMSE score of control group changed before treatment,there was statistical difference before and after treatment(P<0.05).There was no significant difference in ADL score between the two groups before and after treatment.(2)Part two:HT can improve the spatial memory learning ability of APP/PS1 mice.HT can increase the synaptic plasticity in APP/PS1 mice,and reverse the LTP injury in hippocampus of APP/PS1 mice and increase the dendritic spine density in hippocampus.HT can reduce the deposition of A?,reduce the formation of APP and promote the degradation of IDE.At the same time,HT can regulate the alpha and gamma degradation pathway of APP and increase the protein expression of ADAM10,IDE,syn and PSD95.Conclusion:The results show that combination of HT and memantine can delay the progression of dementia and improve the symptoms of Chinese medicine in AD patients.Meanwhile,HT could effectively recover the memory,cognition,thinking ability,self-care and behavior of AD patients.The results showed that HT can improve the cognitive function of APP/PS1 mice,and the underlying mechanism was associated with the deposition of A? in the brain,improve the synaptic plasticity,and increase the level of synaptophysin.