Effect Of Sijunzi Decoction On Aβ-related Transporter In Human Microvascular Endothelial Cells

Alzheimer disease(AD)is a type of central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral damage,which seriously affects people’s health.With the aging of the population in the society,the incidence of AD also continues to rise,but effective preventive drugs are still lacking.The etiology of AD is unclear and the pathogenesis is very complicated.In recent years,drug research based on a single target or mechanism has frequently failed.Therefore,AD research based on new targets and multiple targets has become hot spot.Studies have shown that AD is a metabolic disease related to glucose and lipid metabolism and energy metabolism.TCM believes that the "spleen-transportation" is closely related to metabolism in the body.In recent years,some scholars have proposed "treating from the spleen and stomach" to Alzheimer’s disease,and found that the spleen-invigorating prescription has a certain effect on AD.Sijunzi Decoction is derived from "Taiping Huimin Hefang Prescription",which has the effect of nourishing qi,nourishing qi and strengthening spleen,and is the basic formula for spleen and nourishing spleen.Some studies have shown that Sijunzi Decoction can improve the behavior of AD rats,promote the central energy production of AD rats,and improve the central energy metabolism disorder.However,there is no report on the regulation of Aβ across blood-brain barrier and energy metabolism by Sijunzi Decoction.First,Q-TOF-LC / MS was used to analyze the principal components of Sijunzi Decoction water extract,then the network Pharmacology Method Based on computer system was used to construct the network diagram of component target network and protein action pathway,and the anti-AD effect of Sijunzi decoction was preliminarily predicted.In this study,we used Aβ25-35 oligomer to induce human brain microvascular endothelial cells to simulate AD injury model,and explored the effects of Sijunzi Decoction water extract on Aβ induced cell injury and apoptosis,Aβ trans blood-brain barrier transport related proteins--advanced glycation end product receptor(RAGE),low density lipoprotein receptor related protein(LRP1),and transporters closely related to energy metabolism--glucose transporter 1(GLUT1),glucose transporter 3(GLUT3).The MTT method was used to detect the survival rate of Aβ25-35 induced by Sijunzi Decoction water extract.Real-time quantitative PCR technology and western blot were used to determine the expression of m RNA and protein levels of Sijunzi Decoction water extract.The results showed that Sijunzi Decoction increased the survival rate of injured cells,increased the expression of GLUT1,GLUT3 and LRP1 protein,and decreased the expression of Caspase 3 and RAGE protein.The research results show that the Sijunzi Decoction water extract has protective effect on Aβ-damaged cells,and can regulate the transport of Aβ across the bloodbrain barrier and glucose transport,thereby reducing the abnormal accumulation and deposition of Aβ in the brain,improving brain energy metabolism,and digging for the prevention of AD in later stages Lay the foundation.