The Regulating Effect Of Endothelial Progenitor Cells-derived Exosomes On Vascular Endothelial Cells Inflammation And Oxidative Stress In Type 2 Diabetic Atherosclerosis Mice

Objective: 1.To observe whether type 2 diabetic atherosclerosis is associated with the vascular endothelial cells inflammation and oxidative stress.2.To investigate whether the repair effect of endothelial progenitor cells-derived exosomes(EPC-Exos)on vascular endothelial cells in type 2 diabetic atherosclerosis mice is associated with the regulating effect on vascular endothelial cells inflammation and oxidative stress.Methods: Mice were subjected to type 2 diabetic atherosclerosis model group(MOD group)and control group(CON group).MOD group adopted spontaneous type 2diabetes mellitus db/db mice which were from C57 mice background and fed high-fat diet.CON group adopted C57 mice and fed normal chow.After 14 weeks,MOD group mice were randomly divided into EPC-Exos intervention group(MOD+Exos group)and PBS control group(MOD+PBS group);CON group were randomly divided into EPC-Exos intervention group(CON+Exos group)and PBS control group(CON+PBS group).1 week later,all mice were put to death.Enzyme-linked immuno sorbent assay(ELISA)was used to compare expression levels of serum inflammation index C-reactive protein(CRP),interleukin-8(IL-8)and oxidative stress index superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA).Another oxidative stress index superoxide anion reactive oxygen species(ROS)level was assessed by abdominal aorta ROS fluorescent probe.Results: 1.ELISA detected expression levels of serum inflammatory cytokines:Compared with CON+PBS group mice,CRP expression level increased significantly in MOD+PBS group mice,but IL-8 increased without obvious differences;CRP and IL-8 expression levels all decreased obviously in MOD+Exos group mice compared with the MOD+PBS group mice.2.ELISA detected expression levels of serum oxidative stress index: Compared with CON+PBS group mice,SOD level increased obviously while CAT decreased in MOD+PBS group mice,but MDA increased without obvious differences;Compared with MOD+PBS group mice,SOD and MDA levels all decreased significantly in MOD+Exos group mice;CAT expression level decreased in MOD+Exos group mice compared with CON+Exos group mice.3.Abdominal aorta ROS fluorescent probe: Compared with CON group mice,ROS levels were significantly higher in MOD group mice,while ROS levels decreased in MOD+Exos group mice compared with MOD+PBS group mice.Conclusion:1.Type 2 diabetic atherosclerosis is associated with vascular endothelial cells inflammation and oxidative stress closely.2.EPC-Exos can inhibit vascular endothelial cells inflammation in type 2 diabetic atherosclerosis mice by reducing expressions of CRP and IL-8.3.EPC-Exos can inhibit vascular endothelial cells oxidative stress in type 2 diabetic atherosclerosis mice by reducing expressions of ROS and MDA.4.The repair effect of EPC-Exos on vascular endothelial cells in type 2 diabetic atherosclerosis mice may be associated with reduced damage of blood vessels by inhibiting vascular endothelial cells inflammation and oxidative stress.