| Objective: to explore the protective effect of different intensity exercise intervention on myocardial injury in dB / db mice with spontaneous type 2 diabetes mellitus and its possible mechanism,and to provide experimental data and theoretical basis for clinical intervention of diabetic cardiomyopathy by exercise.Methods: Twenty-four male 16-week-old db/db mice were randomly divided into four groups,6 in each group: model control group(NC group),low intensity exercise group(LE group),medium intensity exercise group(ME group)and high intensity exercise group(HE group).Six non-diabetic wild-type m/m mice of the same age were selected as normal control group(group C).Group C and NC did not intervene,but only did normal physiological activities.The mice in LE group,ME group and HE group were given treadmill exercise for 8 weeks.The mice in LE group,ME group and HE group were given treadmill exercise for 30 minutes five times a week.Before formal intervention,the mice in LE group were given treadmill exercise with increasing intensity for one week.The exercise intensity of LE group was 5m/min,ME group was 10 m/min,HE group was 15 m/min,and the slope of the three groups was 0.After 24 hours of the last exercise,the weight of mice,fasting blood glucose detection(FBG),blood pressure,heart rate,fasting serum insulin(FINS)were measured.Reactive oxygen species(ROS)were detected by DHE fluorescence staining on frozen sections.Myocardial tissue was analyzed by electron microscopy and pathology.Methods The expression of nuclear factor-kappa B(NF-kappa B),recombinant human Sprouty-related EVH1 domain containing protein 1(SPRED1)and vascular endothelial growth factor(Vascular Endothelial Growth Factor(Vascular Endothelial Growth Factor)in myocardium were detected.The expression of microRNA-126 in myocardium was detected by real-time fluorescence quantitative PCR.The results are as follows:1.General changes of db/db mice after exercise Weight: The weight of mice in each group increased significantly at 8W compared with that before intervention(P < 0.01 or P < 0.05);the weight of mice in NC group was significantly higher than that in C group(P < 0.01).Blood Pressure: Within the group,the systolic and diastolic blood pressures of mice in each exercise group decreased significantly after 8 weeks of intervention(P < 0.01 or P < 0.05);between groups,the systolic and diastolic blood pressures in NC group were significantly higher than those in C group(P < 0.01),and at 8 weeks,the systolic and diastolic bloodpressures in LE group,ME group and HE group were significantly lower than those in NC group(P < 0.01 or P < 0.05),while those in ME group were significantly lower than those in NC group(P < 0.01 or P < 0.05).In LE group and HE group(P < 0.05).Heart rate: Compared with the control group,the quiet heart rate of mice in each exercise group decreased significantly after 8 weeks of intervention(P < 0.01 or P < 0.05);the quiet heart rate of NC group was significantly higher than that of C group(P < 0.01),and the quiet heart rate of LE group,ME group and HE group was significantly lower than that of NC group at 8 weeks(P < 0.05).FBG: After 8 weeks of intervention,the fasting blood sugar of mice in each exercise group was significantly lower than that before intervention(P < 0.05);the fasting blood sugar of NC group was significantly higher than that of C group(P < 0.01);the fasting blood sugar of LE group,ME group and HE group was significantly lower than that of NC group at 8 weeks(P < 0.05);and the fasting blood sugar of ME group was significantly lower than that of LE group and HE group(P < 0.05).FINS: After intervention,the serum insulin level in NC group was significantly higher than that in C group(P < 0.01),while that in LE group,ME group and HE group was significantly lower than that in NC group(P < 0.01),and that in ME group was significantly lower than that in LE group and HE group(P < 0.01).2.Pathological changes of myocardial tissue in db/db mice after exercise Electron microscopy: In NC group,the number of mitochondria decreased,the volume increased and the arrangement of mitochondria was disordered,most of the cristae were broken and vacuoles;in each exercise group,the swelling of mitochondria in the cytoplasm was reduced,the number increased,and the cristae shape was basically normal,but in HE group,the myocardial fine fibers were not connected and the lesion dissolved.Masson staining showed that the collagen fibers in NC group were significantly higher than those in C group(P < 0.01),and the collagen fibers in exercise group were significantly lower than those in NC group(P < 0.01),and the collagen fibers in ME group were significantly lower than those in LE group and HE group(P < 0.01).WGA-AF488 staining showed that the area of myocardial cells in NC group was significantly higher than that in C group(P < 0.01),and the area of myocardial cells in exercise group was significantly lower than that in NC group(P < 0.01).The results of alpha-SMA staining showed that the myocardial vascular density of NC group was significantly lower than that of C group(P < 0.01),and that of exercise group was significantly higher than that of NC group(P < 0.01 or P < 0.05),and that of ME group wassignificantly higher than that of LE group and HE group(P < 0.01).3.Inflammatory changes of myocardium in db/db mice after exercise ROS: After the experiment,ROS in NC group was significantly higher than that in C group(P< 0.01);ROS in LE group and ME group was significantly lower than that in NC group(P <0.01).NF-kappa B: After 8 weeks of intervention,the gray value of NF-kappa B protein expression in NC group was significantly higher than that in C group(P < 0.01);the gray value of NF-kappa B protein expression in LE group and ME group was significantly lower than that in NC group(P < 0.05;P < 0.01);and the gray value of NF-kappa B protein expression in ME group was significantly lower than that in LE group(P < 0.05).4.Changes of angiogenesis in myocardium of db/db mice after exercise The expression of microRNA-126: After 8 weeks of exercise,the expressions of circulating microRNA-126 and myocardial microRNA-126 in NC group were significantly lower than those in C group(P < 0.01).The expressions of circulating microRNA-126 and myocardial microRNA-126 in LE group,ME group and HE group were significantly higher than those in NC group(P < 0.01).The expressions of circulating microRNA-126 and myocardial microRNA-126 in ME group were significantly higher than those in LE and HE group(P <0.01).SPRED1 and VEGF: After 8 weeks of exercise,the gray level of SPRED1 protein expression in NC group was significantly higher than that in C group(P < 0.01),the gray level of VEGF protein expression in NC group was significantly lower than that in C group(P < 0.01),the gray level of SPRED1 protein expression in ME group was significantly lower than that in NC group(P < 0.01),and the gray level of VEGF protein expression in LE group,ME group and E group was significantly higher than that in NC group(P < 0.01).In LE group(P <0.01).Research conclusions:1.8 weeks of aerobic endurance exercise with different intensity can protect diabetic myocardium by improving myocardial structure and function,and the effect of moderate intensity is significant.2.The protective mechanism of exercise on diabetic myocardium is related to the microRNA-126/SPRED1/VEGF signaling pathway. |
PDF Full Text Request