AIM To investigate the effects of dexmedetomidine (Dex) pretreatment on myocardial ischemia reperfusion injury (MI/RI) in rats through XIST/miR-125a/DRAM2 axis.
METHODS Forty-five rats were randomly divided into sham operation group, MI/RI group and Dex group. MI/RI rat model was established by ligation of the left anterior descending coronary artery. Dex group was pretreated with intravenous injection of 5 μg/kg Dex before ischemia. H9C2 cardiomyocytes were divided into blank group, H/R group, Dex group, Dex+ pcDNA3.1NC group and Dex+ pcDNA3.1XIST group. In vitro cell model of MIRI was constructed by hypoxia/reoxygenation (H/R). qRT-PCR was used to detect the mRNA expression levels of XIST, miR-125a and DRAM2, Western blotting was used to detect the protein expression of DRAM2 in each group in vivo and in vitro and HE staining was used to detect the myocardial histopathological changes and myocardial infarction size. ELISA was used to determine the contents of creatine kinase isoenzyme (CK-MB) and troponin I (cTnI) in serum of each group and malondialdehyde (MDA) and superoxide dismutase (SOD) detection kit were used to investigate the concentrations of MDA and SOD in the supernatant of cells. The targeting relationship between XIST and miR-125a was investigated by dual luciferase reporter system.
RESULTS In vivo, compared with those in sham operation group, infarct size, CK-MB, cTnI content, XIST and DRAM2 expressions were significantly up-regulated (P<0.05), while miR-125a was significantly down-regulated (P<0.05) in MI/RI group. In addition, compared with those in MI/RI group, infarct size, CK-MB, cTnI content, XIST and DRAM2 expressions were significantly down-regulated (P<0.05), while miR-125a expression was significantly up-regulated (P<0.05) in Dex group. In vitro experiments, compared with those in control group, MDA content, apoptosis rate, XIST and DRAM2 expressions were significantly up-regulated (P<0.05), while SOD content and miR-125a expression were significantly down-regulated (P<0.05) in H/R group. Compared with those in H/R group, MDA content, apoptosis rate, XIST and DRAM2 expressions were significantly down-regulated (P<0.05), while SOD content and miR-125a expression were significantly up-regulated (P<0.05) in Dex group. Over-expression of XIST reversed the protective effect of Dex on MIRI cell models in vitro (P<0.05).
CONCLUSION Dex pretreatment can improve the symptoms of MIRI rats and inhibit the oxidative stress injury and apoptosis of cardiomyocytes, which may be related to the regulation of XIST/miR-125a/DRAM2 axis.
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