Study On The Mechanism Of MiR-27a By Regulating PI3K/Akt Signaling Pathway In Myocardial Ischemia-reperfusion Injury

Object: To explore the mechanism of the phosphatidylinositol-3-kinase/protein kinase B signaling pathway in miR-27a in reducing myocardial ischemia-reperfusion injury in rats,and to explore whether the effect of miR-27a on rat myocardial production is associated with the activation of oxidative stress response.Method: Clean-grade male SD rats,weighing 220-280 g,aged 8 to 10 weeks old,were randomly divided into six groups(n=16): Sham operation group(SP),myocardial ischemia-reperfusion group(I/R group),blank control+I/R group(NC+I/R group),overexpressed miR-27a+I/R group(AAV-miR-27a group),low-expressed miR-27a+I/R group(AAV-miR-27a-antago)and low-expression miR-27a+I/R group + PI3K inhibitor group(LY group).The MI/R model was established by ligation of the left anterior descending branch of the coronary artery for 30 minutes and then reperfusion for 120 minutes.Adeno-associated virus(AAV)was injected into the tail vein for overexpression intervention and low expression intervention.The LY group were injected LY294002(1.5 mg/kg)intraperitoneally 30 min before molding.After 120 min of reperfusion,The serum levels of CK-MB and cTnT were determined by ELISA.The LDH enzyme activity was detected by colorimetry.HE staining was used to observe the pathological changes.Evans blue-TTC staining was used to detect myocardial infarction area.The levels of GSH,SOD and ROS were measured by colorimetric method.Protein levels of PI3K,Akt,p-PI3K and p-Akt were determined by Western blot.Results: Compared with the SP group,the percentage of myocardial infarction area,serum cTnT,CK-MB,LDH were increased,the levels of SOD and GSH were decreased,and MDA level were increased in I/R group(P<0.05).Compared with the I/R group,the percentage of myocardial infarction area,and serum cTnT,CK-MB,LDH in AAV-miR-27a group were increased.The expressions of p-PI3K and p-Akt were down-regulated,and the SOD and GSH levels were decreased,MDA level was increased(P<0.05);Compared with the I/R group,the percentage of myocardial infarction area,serum cTnT,CK-MB and LDH in AAV-miR-27a-antago group were decreased,and the levels of SOD and GSH were increased,MDA level was decreased,and the expressions of p-PI3K and p-Akt were up-regulated(P<0.05).Compared with the AAV-miR-27a-antago group,the percentage of myocardial infarction area,serum cTnT,CK-MB,LDH were increased in the LY group,and the expressions of p-PI3K and p-Akt were down-regulated,and the SOD and GSH levels were decreased,MDA level was increased(P<0.05).Conclusion: Down-regulation of miR-27a expression may alleviate myocardial ischemia-reperfusion injury in rats by activating the PI3K/Akt signaling pathway,thereby inhibiting oxidati8ve stress.