Metabolomics Study Of Urine And Plasma Targets Of APP/PS1 Double Transgenic AD Mice By Moxibustion And Aiwu

BackgroundAlzheimer’s disease(AD)is a chronic degenerative neurological disorder with insidious onset.AD is the most common form of dementia,accounting for 50-60%of all cases.The prevalence of dementia is below 1%in individuals aged 60-64 years,but shows an almost exponential increase with age,so that in people aged 85 years or older the prevalence is between 24%and 33%in the Western world.Representative data from developing countries are sparse,but about 60%of patients with dementia are estimated to live in this part of the world.Alzheimer’s disease is very common and thus is a major public health problem.In 2015,more than 46 million people had dementia,a number that is expected to double every 20 years up to 81 million in 2040 because of the anticipated increase in life expectancy.The main symptoms of AD include:easy to forget the recent events,expression difficulties,disorientation,communication difficulties,difficult to solve common life problems;and indifference,anxiety,manic,depression and other personality changes.Although a great deal of research has been done on AD worldwide,there is still a lack of effective cure for AD.In December,2013,the G8 stated that dementia should be made a global priority and their ambition that a cure or a disease-modifying therapy should be available by 2025.Moxibustion therapy as the characteristic therapy of China,has thousands of years of history,its advantages of clinical operation include:convenient,non-toxic side effects and a certain effect for preventing and treating AD.The preliminary research on AD at home and abroad have proved that moxibustion and moxa smoke can anti-aging by improving oxidative stress,enhance the protection of neurons,anti-apoptptic and the other ways.Metabolomics investigates the activity and status of cellular and organismal metabolism on a global or network scale to delineate the end points of physiology and pathophysiology.It involves the measurement of small-molecule compounds,including endogenous and exogenous molecules,that are the products and substrates of chemical reactions within biological systems.A metabolomics experiment directly reflects the activity of the metabolic network that leads to the production of these metabolites and yields essential information about the underlying biological status of the system in question.Thus,metabolomics is not defined by any particular experiment but reflects the study of metabolism in a comprehensive way.ObjectiveObserving the effects of moxibustion and moxa smoke on the metabolic products of tricarboxylic acid cycle and fatty acid metabolism in urine and plasma of APP/PS1 mice.To explore the different factors of moxibustion in prevention and treatment of AD from energy metabolism mechanism prospective.Methods 36 six-month male mice were randomly divided into 3 groups:moxbustion group,moxa smoke group and model group.And 12 male C57BL/6 non-transgenic mice were used as blank control group.Treatments were given 20mins a day,6 days a week for 8 weeks.In moxibustion group,the moxa stick was aimed above acupoint Guanyuan(CV4).In moxa smoke group,mice were exposed to moxa smoke(10～15mg/m3),while in control group and model group,no treatment was given.Urine samples and plasma samples were collected at the end of 8 weeks.Using GC-MS method to detect the contents of TCA metabolites in urine and UPLC-MS detecting the contents of fatty acids in plasma samples.Results1.Effects on the metabolites of TCA in urine Compared with the model group,the contents of pyruvate,citric acid,malic acid and a-ketoglutarate in urine of moxa smoke group were significantly increased;and the contents of citric acid,a-ketoglutarate,malic acid and fumaric acid in urine of moxibustion group were significantly increased.2.Effects on the metabolites of fatty acids in plasma1)Saturated fatty acids:Compared with the model group,the contents of palmitic acid,nonadecanoic acid,arachidic acid,behenic acid,lignoceric acid,tricosanoic acid showed a significantly decrease in plasma of moxibustion group,but no remarkable changes in moxa smoke group.2)Monounsaturated Fatty Acids:Compared with the model group,the contents of neuronal acid in both moxibustion and moxa smoke groups were significantly increased,but there is no significant difference in contents of palmitoleic acid and oleic acid.3)Polyunsaturated fatty acids:Compared with the model group,the levels of linoleic acid,a-Linolenic acid,eicosadienoic acid,arachidonic acid,EPA,DPA,DHA in plasma of moxa smoke and moxibustion groups significantly increase,and the content of g-Eicosatrienoic acid only increased in moxibustion group.Conclusion1.Moxibustion and smoke can regulate the contents of relevant metabolites in TCA and fatty acid metabolism of AD mice.2.There was no significant difference in levels of markers between the two intervention groups,showing moxa smoke as a main positive factor in moxibustion could delay pathological process of AD.3.The results of the study suggest that,thermal stimulation and moxa smoke can be used as onset factors of moxibustion improve the vivo energy metabolism disorders in AD mice and further delay senescence.