Human umbilical mesenchymal stem cell-derived exosome attenuates car-diac fibrosis in diabetic mice / 中国病理生理杂志

ABSTRACT

AIM:To explore the protective effects of exosome secreted by human umbilical mesenchymal stem cells on cardiac fibrosis in diabetic mouse model.METHODS:Male C57BL/6 mice at 6～8 weeks of age were divided in-to 3 groups randomlycontrol group ,diabetes mellitus(DM)group and DM+exosome group.To develop mouse DM mo-del,the mice were fed with high-fat diet for 5 weeks,followed by intraperitoneal injection of 45 mg/kg streptozocin once a week for 5 weeks.It was considered as a successful DM model that the blood glucose of the mice was ≥16.7 mmol/L.The mice in DM+exosome group were injected with exosome via tail vein.The mice in other 2 groups were injected with saline at the same volume.The heart function was evaluated by color Doppler echocardiography for small animals.The blood sam-ples were collected from abdominal aortas.The blood glucose and non-esterified fatty acids were measured by biochemical colorimetric assay.HE staining was performed to observe the structural changes of myocardial fibers ,and Masson staining was used to observe the cardiac fibrosis.RESULTS:The results of echocardiography showed that left ventricular end-dias-tolic dimension(LVIDd)and left ventricular end-systolic dimension(LVIDs)of diabetic mice were larger than those incontrol mice(P<0.05 and P<0.01,respectively).The ejection fraction(EF)and fractional shortening(FS)decreased in the diabetic mice(P<0.01).Exosome treatment significant decreased the LVIDs(P<0.01),but increased the EF and FS(P<0.01).The blood glucose and non-esterified fatty acids were significantly increased in the diabetic mice.The injection of the stem cell exosome significantly decreased the blood glucose and non -esterified fatty acids(P<0.01).HE staining observation showed that cardiomyocyte hypertrophy and fragmentation of cardiomyocyte in DM group were more se -rious than those in control group.Masson staining showed that the area of fibrosis in DM group was larger than that in con-trol group(P<0.01),but that in DM+exosome group was reduced(P<0.01).CONCLUSION:Exosome secreted by human umbilical mesenchymal stem cells protects the DM model mice from cardiac fibrosis.