Study on the action mechanism of lncRNA MIAT/miR-384-5p in rats with acute myocardial infarction

Objective To investigate the role and molecular mechanism of lncRNA MIAT inhibition in acute myocardial infarction (AMI) in rats. Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into sham, AMI, AMI+si-NC, AMI+si-MIAT, AMI+si-MIAT+miR-NC antagomir, and AMI+si-MIAT+miR-384-5p antagomir groups. The target plasmids were transfected into the myocardial tissue through in situ multi-point injections to silence the expression of lncRNA MIAT and miR-384-5p in rats. After 24 hours of transfection, the AMI model was established by performing ligation of the left anterior descending branch of the coronary artery of the heart for a duration of 24 hours. After completing the modeling, the changes of heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the maximum rate of rise and fall of left ventricular pressure (±dP/dtmax) were gauged by biosignal acquisition system. The 2, 3, 5, triphenyl- 2Htetrazolium chloride (TTC) staining was used to determine the infarct size and the pathological changes in cardiomyocytes were observed by hematoxylin-eosin (HE) staining. The level of serum cardiac troponin-Ⅰ (cTn-Ⅰ) was detected by enzyme-linked immunosorbent assay (ELISA). Transmission electron microscope (TEM) was used to observe the number of autophagosomes. Reverse transcription-quantitative polymerase chain reaction (RTqPCR) was used to detect lncRNA MIAT and miR-384-5p gene expression, and western blotting was used to detect autophagy-associated proteins Beclin1, Cathepsin D and LC3 expression. Results Compared with the sham group, the expression of lncRNA MIAT was increased in rats with AMI (P < 0.01). Compared with the AMI+siNC group, the knockdown of lncRNA MIAT led to an upregulation of miR-384-5p expression, an increase in the levels of HR, LVSP and +dp/dtmax, and a decrease in the levels of LVEDP and -dp /dtmax. TTC and HE staining revealed a decreased myocardial infarct size in AMI rats and improved cardiomyocyte morphology. Additionally, serum cTn-I levels were significantly reduced, the number of autophagosomes was decreased, and the protein expression levels of Beclin1, Cathepsin D, and LC3 were down-regulated (all P < 0.05). The above effects of lncRNA MIAT knockdown were significantly reversed when co-administered with the miR-384-5p antagomir (all P < 0.05). Conclusion Inhibition of lncRNA MIAT can alleviate AMI in rats, which is related to upregulation of miR-384-5p expression and inhibition of autophagy.