Résumé
Objective To study the expression of interleukin-17 (IL-17) in diabetic rat aorta and the effect of intervention with resveratrol,meanwhile,to explore the potential mechanisms of IL-17 induced diabetic vascular diseases and the protective role played by resveratrol in the epigenetic field.Methods The experiment was carried out in 4 groups:normal control group(NC),normal interventional group(NB),diabetic group(DM),and diabetic interventional group(DB),NB and DB groups were intervened with resveratrol.Immunohistochemistry was used to observe the histological localization of IL-17 and to measure the thickness of rat abdominal aorta.Western blotting,real-time PCR,and methylation-specific PCR were used respectively to compare the expression of IL-17 protein and mRNA,as well as DNA methylation in 4 groups.Results IL-17 mainly expressed in arterial intima of diabetic rats,the abdominal aorta in DM group was obviously thicker than that in NC and DB groups(P＜0.05).IL-17 protein and mRNA expressions in DM group were significantly higher than NC group(P＜0.05),and were reduced in NB and DB groups compared with NC and DM groups respectively.While DNA methylation levels of IL-17 in DM group were significantly lower than NC group(P＜0.01),however,the levels in NB and DB groups were elevated accordingly as compared with corresponding groups.Conclusions The increased levels of IL-17 in aorta of diabetic rats suggests that IL-17 is involved in the process of inflammatory responses to diabetic macrovascular diseases,while resveratrol could inhibit the expression,it may play a role in protecting aorta,and the regulation of IL-17 gene promoter DNA methylation levels may be the potential mechanism underlying these two phenomena.
Résumé
The concept of epigenetics was first proposed by Waddington in 1942,referring to phenotypic changes that are not related to the underlying DNA sequence,yet alterations in the level and function of gene expression can be heritable,such as DNA methylation,histone modifications,microRNA interference,etc.Phenotype changes while genotype remains unchanged,this controlled mechanism can be kept stable throughout cell division,proliferation,and subsequent process of development.This process thus may cause corresponding changes in the pathophysiology,which are correlated with the occurrence of cancer,immune disorder,cardiovascular disease,metabolic syndrome and so on.Diabetes mellitus is the third heaviest chronic diseases in the world,and does serious harm to human health,especially the diabetic vascular diseases.Even if the blood glucose level is controlled in an ideal state,vascular inflammation still persists,indicating the existence of metabolic memory.Studies have suggested that the pathogenesis can be elucidated at the level of epigenetics.This paper mainly focuses on DNA methylation,histone modifications,and is an overview of epigenetics research progress in diabetic vascular diseases.