The Relationship Between Aggravation Of Myocardial Injury?FUNDC1 And Autophagy After Myocardial Infarctionin Diabetic Rats

Objective:By observing the changes of infarct size,cell morphology and ultrastructure,dephosphorylated FUNDC1 and LC3-II in normal and diabetic rats after myocardial infarction,the relationship between the aggravation of myocardial injury and FUNDC1 and autophagy in diabetic rats after myocardial infarction was explored.Methods:Healthy and clean male SD rats,weighing about 200~230g and aged from 2 to 3 months,were injected intraperitoneally with low concentration(50mg/Kg)streptozotocin(STZ)to prepare the diabetic rat model.Thirty diabetic rats were selected by random number table method and divided into two groups(n=15): sham operation group(DS group)and myocardial infarction group(DI group).In addition,30 experimental rats were bred simultaneously and divided into 2 groups(n=15)according to the principle of random control: normal rats sham operation group(NS group)and normal rats myocardial infarction group(NI group).The left anterior descending coronary artery(LAD)was ligated by thoracotomy in the NI group and DI group,and the LAD was not ligated in the NS and DS groups.Five rats in each group were randomly selected to measure the myocardial infarction area by TTc method 6h after myocardial infarction.The remaining 10 rats in each group were sacrificed 6h after myocardial infarction and the myocardial tissue in the infarct area was taken.The ultrastructure of mitochondria and the number of autophagosomes were observed under electron microscope.Using Western blot method determination of myocardial FUNDC1 to phosphorylation level and the expression of Lc3-?.Results:Compared with the NS group,the difference in myocardial infarction area in the DS group was not statistically significant(P > 0.05),while the myocardial infarction area increased in the NI group and DI group(P <0.05).Compared with the DS group,the myocardial infarction area increased in the NI group and DI group(P<0.05).Compared with the NI group,the myocardial infarction area increased in the DI group(P<0.05).Compared with the NS group,there was no statistically significant difference in the dephosphorylation of FUNDC1 in the DS group(P > 0.05),and increased dephosphorylation in the NI group and DI group(P <0.05).Compared with the DS group,the dephosphorylation of FUNDC1 increased in the NI group and DI group(P<0.05).Compared with the NI group,the dephosphorylation of FUNDC1 increased in the DI group(P<0.05).Compared with NS group,lc3-II increased in DS group,NI group and DI group(P<0.05).Compared with DS group,lc3-II increased in NI group and DI group(P<0.05).Compared with the NI group,lc3-II increased in the DI group(P<0.05).Compared with the NS group,the damage of myocardial pathology and ultrastructure was aggravated in the DS group,but the number of autophagic bodies was not significantly increased.The damage of myocardial pathology and ultrastructure was aggravated in the NI group and DI group,and the number of autophagic bodies was increased.Compared with DS,the damage of myocardial pathology and ultrastructure was aggravated in the NI group and DI group,and the number of autophagosomes was increased.Compared with the NI group,the myocardial pathological and ultrastructural damage was aggravated in the DI group,and the number of autophagosomes was decreased.Conclusion:Myocardial tissue damage in infarcted area of diabetic rats is aggravated after myocardial infarction.The mechanism may be related to the inhibition of FUNDC1 dephosphorylation and the reduction of autophagy by diabetes mellitus.