The Effect And Mechanism Of MiR-222 Induced By Exercise In The Protection Of Diabetic Myocardium

Chapter 1 Changes of cardiac structure and cardiac function in diabetic patientsObjectiveTo investigate the changes of cardiac function and myocardial structure in patients with diabetes mellitus,so as to make clear the specific myocardial damage caused by chronic hyperglycemia.Methods615 diabetic patients were randomly included,the patients were divided into two groups according to cardiovascular complication:simple diabetes group(DM group)and with the cardiovascular complications group(DM+CAD group),recorded the clinical data,myocardial structure and cardiac function of the patients.Results(1)The age,course of disease,systolic blood pressure(SBP)and fasting C peptide of the DM+CAD group were significantly higher than the DM group(P<0.05),but heart rate,glycosylated hemoglobin,fasting blood glucose and postprandial blood glucose were lower than the DM group(P<0.05).(2)The left atrial diameter,left ventricular end diastolic diameter,interventricular septal thickness and left ventricular posterior wall thickness in DM+CAD group were significantly higher than DM group(P<0.05).(3)The levels of SBP,BMI and fasting C peptide in diabetic patients were positively related to left atrial diameter,interventricular septal thickness and left ventricular posterior wall thickness(P<0.05).And HbAlc was negatively correlated with left ventricular ejection fraction(LVEF)and left ventricular shortening fraction(LVFS)(P<0.05).ConclusionProlonged high glucose can cause enlargement of the heart cavity,thickening of the ventricular wall,and structural remodeling of the heart.Strengthening blood glucose control and reducing HbAlc is one of the important measures to prevent diabetic complications.Chapter 2 Study on the myocardial protective effects of exercise in diabetic mice and its correlation with miR-222ObjectiveThe purpose of this study was to investigate the relationship between microRNA 222(miR-222)and the myocardial protective effects of exercise in diabetic mice,exploring the effect of miR-222 on the cardiac expression of PTEN,phosphatidylinositol 3 kinase(PI3K)and protein kinase B(PKB or Akt)in diabetic mice.Methods36 C57BL/6 male mice were randomly divided into normal control group(NC group,n=16)and DM model group(DM group,n=20).After establishing the DM model,the rats were divided into 4 subgroups based on NC and DM group,that is,normal non-exercise group(Con-Se,n=8),normal exercise group(Con-Ex,n=8),diabetics non-exercise group(DM-Se,n= 10)and exercise diabetic group(DM-Ex,n=10).After 5 weeks swimming exercise intervention,heart ultrasonic diagnostic apparatus was used to measure the cardiac function;The pathological changes of myocardium were observed under light microscope;RT-PCR was used to measure the level of miR-222,ANP and ?-MHC mRNA in myocardial tissue.Western blot was used to determine the related protein in myocardium.Results(1)The LVEF and LVFS in DM-Se group were lower than NC group and DM-Ex(all P<0.05);(2)There was no pathological change of myocardial tissue in NC group,but pathological changes were observed in DM group,and DM-Se group was more severer.(3)Compared with NC group,the levels of myocardial ANP and ?-MHC mRNA in the DM mice were significantly increased(P<0.05),and the result showed that these fetal gene mRNA were significantly decreased in the DM-Ex group compared with DM-Se group(P<0.05).(4)After the exercise intervention,the expression of myocardial miR-222 was increased,that is,both Con-Ex and DM-Ex group were higher than their corresponding non-exercise group(all P<0.05)(5)Compared with Con-Se group,the expression of myocardial PTEN protein increased in DM-Se group and DM-Ex group,the increase was more pronounced in DM-Se group(P<0.05).(6)Compared with Con-Se group and DM-Se group,the cardiac expression of PI3K(p85),PI3K(p110a)and p-Akt protein was lower in DM-Se(P<0.05).ConclusionExercise training can alleviate the pathological changes of heart induced by high glucose,and improve cardiac function in diabetic mice;MiR-222 induced by exercise training may play a role in the regulation of PI3K/Akt signaling pathway by negatively regulating PTEN expression.