Discussion On The Mechanism Of The Nourishing Yin Benefiting Vital Energy Activating Blood Method Attenuates Metabolic Memory Of KKAy Mice With Diabetic Macroangiopathy Based On DNA Methylation

Objective:The oxidative stress from hyperglycosemia leads to metabolism memory.It is presumed that ShenQi Compound Recipe,which has the function of supplementing Qi and Yin, with activating blood, could retard oxidation to obstruct the metabolism memory to protect the great vessels.TO investigate the mechanism with epigenetics DNA methylation to explain the principle and expand the range of medication target point.Methods:273male KKAy mice,7-8weeks old, after1week, were divided to model groups.contains KKAy model group (KKAy MG); ShenQi compound recipe low-dosage group(SQCRL); ShenQi compound recipe middle-dosage group (SQCRM); ShenQi compound recipe high-dosage group(SQCRH);Metformin group.The KKAy CG were fed with normal diet, while others with high fat diet for8weeks.After successful modeling Metabolic Memory of KKAy Mice with Diabetic Macroangiopathy,with KKAy CG and KKAy MG NS10ml·kg-1·d-1, SQCRL28.8g·kg-1·d-1,SQCRM14.4g·kg-1·d-1,SQCRH7.2g·kg-1·d-1,Metformin group0.167g·kg-1·d1.In the experimental period, general statuswere observed as well as the fast blood glucose. The8-10mice were sacrificed to detect the fasting blood glucose, insulin, lipid levels, ELIS A, HE Staining in thoracic aortic, AI, Immunohistochemical indicators form different course of treatment.By DNA Methylation technique, Screening the differentially expressed genes,using GO annotations and Pathway analysis, explaining the biological significance.Results:SQCRM and Metformingroup were better than that other group in general status, blood glucose, blood lipid, oxidative stress index, HE pathological staining,immunohistochemical and cell apoptosis.By GO annotation and Pathway analysis, mainly involving Tnf, mTOR, Nrf2, Gpxl, AMPK genemethylation, etc.Conclusion:SQCRM and Metformin group can improve general status, improve lipid metabolism disorder, reducing oxidative stress, protecting macroangiopathy,blocking the metabolic memory in KKAy mice.Especially SQCRM is significant.The genemethylation,which selectively inhibit of IGF-PI3K-Akt-TSC2-mTORC2signaling pathway,is the possible mechanism of blocking metabolic memory,preventing and curing diabetes; Tlr4, Tnf gene methylation, blocking the Tlr4/NF-K B signaling pathway and Nrf2gene methylation, activation of the pathway of anti oxidative stress Nrf2/ARE, also have particular concern with this.