Metabonomics-based Study On The Biological Mechanism Of Kidney Deficiency And Essence Deficiency In Alzheimer’s Disease And The Interventional Effect Of Dihuang Yinzi Decotion

Objective:From the perspective of metabolism,explore the partly biological mechanism of AD kidney deficiency and essence deficiency syndrome and the mechanism of Dihuang Yinzi Decotion’s intervention in AD kidney deficiency essence deficiency syndrome.Methods:1.Replication of the model of AD kidney deficiency and essence deficiency:Intraperitoneal injection of D-galactose combined with sexual intercourse was used to construct a model of kidney deficiency and essence deficiency.On the basis of the model of kidney deficiency and essence deficiency,an AD disease model was prepared by intracerebroventricular injection of Aβ_1-42.2.Validation of AD kidney deficiency and essence deficiency syndrome model:Morris water maze behavior combined with the determination of serumβ-amyloid and Tau protein content to verify the AD disease model;to detect the levels of malondialdehyde,catalase,and serum testosterone,which are related to antioxidant capacity,to verify the syndrome model of kidney deficiency and essence deficiency3.Proton nuclear magnetic resonance and liquid chromatography-mass spectrometry were used to detect the changes of metabolites in serum,urine,and hippocampus under the condition of AD kidney deficiency and essence deficiency and Dihuang Decotion’s intervention.Results:1.Model verification:（1）AD disease model verification:Morris water maze behavior test results showed that the learning and memory ability of AD rats in the kidney deficiency and essence deficiency group was decreased,and the levels ofβ-amyloid and Tau protein in the body increased;（2）kidney deficiency and essence Validation of the deficiency syndrome model:The content of malondialdehyde in the AD kidney deficiency and essence deficiency syndrome group increased,and the contents of catalase and testosterone decreased.2.Find out a total of 14 different metabolites in the serum of AD rats with kidney deficiency and essence deficiency,the contents of valine,isoleucine,lactic acid,alanine,acetoacetate,leucine,and methionine increased in serum of rats with AD kidney deficiency and essence deficiency,the content of very low density lipoprotein/low density lipoprotein,N-acetylglycoprotein,choline,phosphocholine,glycine,β-glucose,andα-glucose decreased.After the intervention of Dihuang Yinzi Decotion,the content of very low density lipoprotein/low density lipoprotein,N-acetylglycoprotein,choline,phosphocholine,β-glucose,andα-glucose increased,the content of valine,isoleucine acid,lactic acid,alanine,acetoacetic acid,leucine,and methionine decreased.3.Find out a total of 16 different metabolites in the urine of AD rats with kidney deficiency and essence deficiency,the content of methylmalonic acid,lactic acid,butyric acid,N-acetylglycoprotein,O-acetylglycoprotein,acetoacetic acid,α-ketoglutarate,citric acid,creatinine,phenylacetylglycine,alanine,and trimethylglycine increased in urine of rats with AD kidney deficiency and essence deficiency,the content of acetic acid,dimethylamine,taurine,and hippuric acid decreased.After the intervention of Dihuang Yinzi Decotion,the content of acetic acid,dimethylamine,taurine,hippuric acid increased,the content of methylmalonic acid,lactic acid,butyric acid,N-acetylglycoprotein,acetoacetic acid,α-ketoglutarate citric acid,creatinine,phenylacetylglycine,alanine,trimethylglycine decreased.4.Find out a total of 15 different metabolites in the hippocampus of the AD kidney deficiency and essence deficiency,the contents of creatine,DL-lactic acid,DL-alanine,ascorbic acid,proline,histamine,and palmitamide in the hippocampus of the AD kidney deficiency syndrome group increased,and hypoxanthine,L-Phenylalanine,xanthine,L-norleucine,DL-tryptophan,acetyl-L-carnitine,D-pantothenic acid,and DL-malic acid are reduced in content.After the intervention of Dihuang Yinzi Decotion,the contents of L-phenylalanine,L-norleucine,and DL-tryptophan increased,while the contents of creatine,DL-lactic acid,DL-alanine,ascorbic acid,and histamine decreased.Conclusion:1.14 differential metabolites in serum,16 differential metabolites in urine,and 15differential metabolites in hippocampus were detected in AD rats with kidney deficiency and essence deficiency;2.AD kidney deficiency and essence deficiency syndrome has abnormalities in glucose metabolism,lipid metabolism,amino acid metabolism,intestinal microbial metabolism,neurotransmitter metabolism,and vitamin metabolism.Among them,energy metabolism disorders are the main manifestations;3.Dihuang Yinzi Decotion can correct glucose metabolism,lipid metabolism,amino acid metabolism,intestinal microbial metabolism,neurotransmitter metabolism,and vitamin metabolism abnormalities,and improve the body’s energy metabolism to play a therapeutic effect on AD kidney deficiency and essence deficiency syndrome.