| Background Once the acute myocardial infarction happened,timely medication treatment or percutaneous coronary intervention are needed to make the flow regains to myocardial tissues has became the efficient measures to save life.But restoration of blood flow to ischemic myocardium can re-establish metabolic and ionic homeostasis,However,reperfusion following prolonged ischemia can also lead to irreversible damage,and make more injure than the benefits came from the restoration of blood flow.Temporarily decrease the mortality of acute myocardial infarction,but the the risk of heart failure dramatically increase.Thus,Treatment measures for acute cardiovascular disease should both focusing on restoration of blood flow to ischemic myocardium and reducing the ischemia-reperfusion.Recently,another potential therapeutic target that has emerged to treat myocardial ischemia-reperfusion is micro RNA.And PI3K/Akt signaling pathway as a important survival pathways in cells,its after ischemia-reperfusion myocardial protection has long been recognized.And we found that a variety of micro RNA making heart protection work by activating the PI3K/Akt pathway.Objectives1.To investigate the cardioprotective effect of miRNA-499 in myocardial ischemia-reperfusion injury after acute acute myocardial infarction happened.2.Whether the miRNA-499 play its cardioprotective role in myocardial ischemia-reperfusion by activating PI3K/Akt signaling pathway.Methods1.Model and grouping Thirty SD rats were randomly divided into shamoperation group,then myocardial ischemia-reperfusion injury(MIRI)group and myocardial ischemia-reperfusion injury with miRNA499 agomir preconditioning(agomir)group.Coronary artery was not ligatured in the sham-operation group;MIRI group built myocardial ischemia-reperfusion modles with left anterior descending coronary artery ligation for 30 min,loosen the ligature 2 h;agomir group injected miRNA499 agomir 48 hours before building myocardial ischemia-reperfusion modles.2.MiRNA-499 and the mRNA Ievel of phosphatidylinositol 3-kinase(P13k)and were determined by RT-PCR.3.Using Western blot to test the expression of Akt and Phosphorylated Akt(p-Akt).4.The myocardial infarction size of each group was stained by TTC.Results1.The expression of mi R-499 of each group :As compared with sham-operation group,the expression of miRNA-499 in MIRI group were significantly decreased(P<0.01);compared with MIRI group the expression of miRNA-499 in agomir group were significantly increased(P<0.01),and when compared with sham-operation group the expression of mi R-499 was significantly increased too(P<0.01).2.The expression of PI3K in each group: Comparing MIRI group with sham-operation group,the mRNA Ievel of PI3K were significantly decreased(P<0.01)。Compared with MIRI group,the expression the mRNA Ievel of PI3K in agomir group were higher(P<0.01),but the expression of PI3K was decreased(P<0.01)when compared with sham-operation group.3.The phosphorylation activity of Akt of each group: the phosphorylation activity of Akt of each groupby the ratio of P-Akt and Akt,Comparing MIRI group with sham-operation group,the phosphorylation activity of Akt were significantly decreased(P<0.01)。Compared with MIRI group,the the phosphorylation activity of Akt in agomir group were higher(P<0.01),and when compared with sham-operation group it is also highter(P<0.01).4.The infarction size of each group The infarction size was significantly increased in MIRI group when compared with sham-operation group(P<0.01),when compared with sham-operation group the infarction size of agomir group was higher(P<0.01)but it was significantly decreased when compared with MIRI group(P<0.01).Conclusions1.As we compare the sham-operation group,MIRI group and agomir group we found that as compared with sham-operation group,the expression of miRNA-499 and the mRNA Ievel of PI3K in MIRI group were significantly decreased,and although the agomir group built the myocardial ischemia-reperfusion modles too,but with the upregulation of miRNA499 by preconditioning of miRNA499 agomir,the expression of mi R-499 were significantly increased not only when compared with MIRI group,but also higher when compared with sham-operation group,all of these show that the miRNA499 agomir do improve the expression of miRNA499.2.Compareing the infarction size of sham-operation group,MIRI group and agomir group after TTC,The infarction size of MIRI group was significantly increased when compared with sham-operation group,but although the agomir group built the myocardial ischemia-reperfusion modles too,but its infarction size was significant decreased when compared with MIRI group,and there was no infarction size in sham-operation group,these prove that mi R-499 can reduce the myocardial ischemia-reperfusion induced by restoration of blood flow after acute myocardial infarction3.The expression PI3K mRNA and phosphorylation activity of Akt of sham-operation group,MIRI group and agomir group were proportiona with the expression of mi R-499,which indicate that mi R-499 can reduce myocardial ischemia-reperfusion via activating the PI3/Akt signaling pathway. |
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