Yangyin Yiqi Huoxue Method Regulates MAPK Signaling Pathway To Block The "metabolic Memory" Of Diabetic Macroangiopathy GK Rats

Objective:This study used oxidative stress as the entrance to observe Nourishing Yin Benefiting Vital Energy Activating Blood method effects of ShenQi compound recipe on GK rats with diabetic Macroangiopathy through influence blood glucose, serum CHOL,8-iso-PGF2a; Thoracic aorta homogenate SOD, MDA, aortic pathological morphology, cell apoptosis, analysis dose-time-effect relationship, infering that it may via inhibiting oxidative stress and blocking "metabolic memory" way to protect vascular. Application of gene chip technology for molecular targets of Shen Qi compound to prevente and cure diabetic macrovascular disease, to investigate the "metabolic memory" of biological effect and mechanism of Nourishing Yin Benefiting Vital Energy Activating Blood method, so as to provide a theoretical basis for the clinical application of Traditional Chinese Medicine in preventing and treating diabetic macrovascular disease.Methods:160GK rats were given 1 week adaptive feeding, according to blood glucose value level from high to low were randomly divided into model group and Shen Qi compound high dose group (Shen high group), Shen Qi compound middle dose group (Shen middle group), Shen Qi compound low dose group (Shen low group), metformin group (Western Medicine group) (n=32), given high fat diet; Wistar Group(control group)32 rats were given common feed.Each group was continuoued feeding for 12 weeks.The "metabolic memory" model of diabetes was established. After modeling, model group and control group were given 5ml/kg.d saline gavage, Shen high group was given 2.88g/kg.d Shen Qi compound extract gavage, Shen middle group was given 1.44 g/kg.d Shen Qi compound extract, Shen low group received 0.72 g/kg.d Shen Qi compound extract, the western medicine group was given 0.1 g/kg.d dimethyl biguanide gavage, therapeutic intervention for 16 weeks. During the experiment, from the overall level of observation, general conditions of rats, monitoring the changes of FPG. Rats in each group were executed at 8,16 weekend after irrigation, detection of CHOL, thoracic aorta homogenate SOD, MDA and other indicators; from the level of organization and detection of thoracic aortic cell apoptosis. HE staining of aorta was used to observe the morphology; observation in different time windows, different interventions on rat model of metabolic memory effect. Using gene chip technology to the thoracic aorta for examination of the gene expression profiles. We screened the differentially expressed genes, GO notes, Pathway analysis, explain the biological significance.Results:Effects of Shen middle group is better than Shen high group and Shen low group, which can significantly improve the general condition of the GK rats, blood glucose, blood lipids, oxidative stress index, aortic pathological morphology and apoptosis. Shen middle group and model group, the difference expressed genes by GO annotation, pathway analysis, mainly involving macromolecules metabolic process, cell death, signal transduction, cell migration and MAPK signaling pathway, sonic hedgehog signal transduction pathway, Notch signaling pathway, insulin signal transduction pathway; related to the gene Csnkld, Lama4, Elav11, abi1, Anxa1, Nsg1 and so on.Conclusion:Shen middle group can better improve the general state of GK rats with diabetic macroangiopathy, lower blood suger,improve lipid metabolism, reduce oxidative stress, protecting vascular endothelial injury in rats, blocking the "metabolic memory". The mechanism is through regulation of the macromolecules metabolic process, cell death, signal transduction, cell migration and MAPK signaling pathway, sonic hedgehog signal transduction pathway, Notch signaling pathway, insulin signal transduction pathway and Csnkld, Lama4, Elav11, abi1, Anxa1, Nsg1. Based by promoting endothelial cells to repair of the damaged early diabetic macro-angiopathy to improve oxidative stress in vascular damage. ShenQi compound recipe maybe through the regulation of MAPK signaling pathway, reduce oxidative stress, inhibit of apoptosis, eliminate inflammation, blocking the "metabolic memory" to prevent and treat of diabetic macroangiopathy.