The Research Of ShenQi Compound Recipe On The Relationship Of The Dose-Eeffect-Time In KKAy Mice With Diabetic Macro-angiopathy And The Epigenetic Mchanisms

Objective:Through observing the effect of ShenQi Compound Recipe which has the function of supplementing Qi and Yinand promoting the blood circulation,on the aortic pathological morphology,aortic apoptosis, aortic apoptosis, blood lipids, blood glucose, blood oxLDL, blood3-NT,8-iso-PGH2α and the protein expression of TNF-a,mTOR and MIP-2;andinvestigatingthe molecular targetsand the mechanisms of prevention and treatment of diabetic macroangiopathies, by using DNA methylation technologyof the epigenetics,providing the theoretical basis of TCM inprevention and treatment ofdiabetic macroangiopathies.Methods:273male KKAy mice,7-8weeks old,were divided to six groups:the Blank group,the model group,the ShenQi Compuound Prescription high-dosegroup,the the ShenQi Compuound Prescription dosegroup,the ShenQi Compuound Prescription low-dosegroup,the metformin group.The control group were fed with normal diet,and other groups were fed with high fat diet for eight weeks after adaptive feeding for four weeks to result in diabetic vascular disease model.And then the model group were given10ml/kg.d saline gavage,the ShenQi Compuound Prescription high-dosegroup were given ShenQi compound recipe with28.8g/kg.d,theShenQi Compuound Prescription dosegroup were given ShenQi compound recipe with14.4g/kg.d,the ShenQi Compuound Prescription low-dosegroup were given ShenQi compound recipe with7.2g/kg.d,the metformin group were given metformin with0.167g/kg. d.During the experiment the general conditions were observed as well as the water intake, food intake, body weight and blood glucose.Each group was randomlyselected five KKAy mices to detec serumlipids, oxLDL,3-NT,8-iso-PGH2a,vascular apoptosis,HE Staining in abdominal aortic for observing aortic morphology,the level of TNF-α,mTOR and MIP2by using immunohisto-chemical.The different methylated genes were got with the help of DNA methylation technology, then relevant literature about the genes in the NCBI database and explain its biological significance by using GO enrichment and pathway analysis. Results:the ShenQi Compuound Prescription dosegroupcan significantly mitigate the symptoms of drinking and eating more, reduce body weight,the level of TC, oxLDL,3-NT,8-iso-PGH2a,the endothelial cell apoptosis and the protein expression of the TNF-a, mTOR,MIP-2.We found some representative hypermethylated genes: mTOR, Tnfrsflb, Ppargclα, Tlr5, Alox12, CYP24A1, TCF4, HB-EGF, Tnfaip8by comparing the ShenQi Compuound Prescription dosegroup to the model group and the time of the sixth week to the third week.The functions of these genes include cellular processes, metabolic processes, cell killing and immune response.Conclusion:The ShenQi Compuound Prescriptiondosegroup is better to improve the general state of KKAy mice, reduce their drinking water, food intake, body weight, lipid deposition,then ruduse the endothelial cells damage caused by the inflammatory reaction,protect endothelial cells,extenuateoxidative stress response,improve the pathological state of the aorta,reduce the protein expression of the TNF-a, mTOR, MIP-2.The molecular mechanisms of the protecting diabetic vascular disease by the ShenQi Compuound Prescription dosegroupmay be associated with DNA methylation.The hypermethylatedgenes involve reducing oxidative stress, protecting vascular endothelial cells, inhibition of vascular smooth muscle cell proliferation and reducing insulin resistance.The hypermethylatedtumor-related genes prompt that the ShenQi Compuound Prescrip play an important sole in the tumorigenesis.