Relationship between miR-27a and SIRT1 during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between microRNA-27a (miR-27a) and silent information regulator 1 (SIRT1) during myocardial ischemia-reperfusion (I/R) in rats.Methods:Fifty clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 5 groups ( n=10 each) by the random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), AAV9-miR-27a overexpression + myocardial I/R group (AAV+ I/R group), miR-27a antagomir + myocardial I/R group (AG+ I/R group) and AAV9-miR-27a negative control+ myocardial I/R group (NC+ I/R group). The myocardial I/R injury model was prepared by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion. At day 14 before ischemia, AAV9-miRNA-27a adeno-associated virus 2×10 11 v. g was injected via the tail vein in AAV+ I/R group, and AAV9-miR-27a NC 2×10 11 v. g was injected via the tail vein in NC+ I/R group. miR-27a antagomir 10 mg/kg was injected via the tail vein once a day at 3 days before ischemia in AG+ I/R group. At the end of 120 min of reperfusion, serum cardiac troponin T(cTnT), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH) concentrations and contents of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissues were determined by enzyme-linked immunosorbent assay, the percentage of myocardial infarct volume by TTC staining, the expression of miR-27a in myocardial tissues by quantitative real-time polymerase chain reaction, and the expression of SIRT1 in myocardial tissues by Western blot. Results:Compared with Sham group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in AAV+ I/R, and the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05), and no significant change was found in the parameters mentioned above in NC+ I/R group ( P>0.05). Compared with AAV+ I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05). Conclusions:miR-27a is involved in the pathophysiological mechanism underlying myocardial I/R injury probably through inhibition of SIRT1 expression in rats.