Protective Effect And Mechanism Of Umbilical Cord Mesenchymal Stem Cells On Macrovascular Disease In Mice With Type 1 Diabetes Mellitus

OBJECTIVE: By using umbilical cord mesenchymal stem cells(h UCMSCs)in mice with type 1 diabetes mellitus,we observe the effect of the treatment of diabetic macroangiopathy in T1 DM mice and explore the effect of h UCMSCs on reducing vascular endothelial cell damage and the possible mechanismthe in T1 DM mice.To provide ideas for the treatment of diabetic macrovascular disease.METHODS: After diagnosing T1 DM,the experimental mice were randomly divided into the following groups,and given the corresponding intervention measures.(1)Diabetic group:There are not any interventions after the onset of the disease in this group;(2)Group Insulin:Mice in this group were treated with Glargine,according to the situation of blood glucose to adjust the amount.(3)Group h UCMSCs:Mice in this group were treated with an intravenous infusion of h UCMSCs through vena caudalis after diagosis.(4)Group Normal Control:NOD mice without diagosis were selected as normal control group after 8 weeks of detection.The day of onset as day 0,and the body weight was weighed and the blood glucose was measured,then measured every 7 days.Eight weeks after the onset of the mice,the mice were sacrificed and the whole blood vessels were taken.HE staining was used to observe the atherosclerotic lesions.ELISA was used to detect the expression of AGEs in tissues.Real-time PCR was used to detect the tissues.m RNA expression of RAGE,P65,IL-6,and VCAM.Results:(1)General conditions: After the diagnosis of diabetes,all groups of mice developed more food,more drink,and more urine.The mice in the normal group had good growth and mental status,were active,and had shiny hair.The diabetic control group showed obvious dullness,less movement,and dull response compared with other groups.(2)Change in body weight: Body weight of mice in normal group did not change significantly,body weight of mice in diabetes group continued to decrease,h UCMSCs treatment group,body weight in early stage of disease decreased significantly,weight recovered afterwards,and had returned to normal group mice by the end of the experiment.The body weight of the insulin group was basically stable;(3)Blood glucose changes: On the first day of disease,h UCMSCs treatment group,insulin group,and control group had significantly higher blood glucose levels than the normal group.On the 56 th day after onset,the insulin group and stem cells There was no significant difference between the blood glucose level and the normal group.Diabetic mice showed a sustained hyperglycemic state;(4)HE staining of aorta in each group: HE staining revealed that the normal group of mouse aortic endothelial cells were regular,well-arranged,and smooth.There was no thickening of the media,but in the diabetic mice,the aortic wall was unclear and disorganized.Endothelial cell damage,bulge,irregular morphology,and thickening of the media of the blood vessels were observed.In the h UCMSCs-treated mice,the aorta of the mice was better than the diabetic group and insulin.The lesions of the mice were significantly reduced,indicating that h UCMSCs treatment has a protective effect on diabetic macroangiopathy;(5)ELISA assay Endothelial AGEs expression: AGEs were highest in the diabetic group and lowest in the normal group.The expression of AGEs in the mesenchymal stem cells group was significantly lower than that in the diabetic group(P<0.05),while the stem cells group and the insulin group AGEs.There was no significant difference in the expression of the expression(P>0.05).(6)The results of Real-time PCR showed that the RAGE,IL-6,VCAM-1,and P65 expressions were highest in the diabetes group and were normal.The expression of AGEs in the mesenchymal stem cell group was significantly lower than that in the insulin group and the diabetic group,and the difference was statistically significant(P>0.05).CONCLUSIONS:(1)Umbilical cord mesenchymal stem cells can reduce the damage of vascular endothelium,delay the atherosclerosis of vascular endothelium,and protect large vessels of diabetes.(2)Umbilical cord mesenchymal stem cells reduce the damage of vascular endothelium in NOD mice by inhibiting the expression of AGEs/RAGE induced by hyperglycemia,reduce the incidence of vascular atherosclerosis.