Objectives The present study was designed to investigate the effect of liver X receptors (LXRs) on ischaemia reperfusion induced injury in isolated rat heart and to explore the mechanism whether attenuate the ischaemia reperfusion injury by improving myocardial energy metabolism.
Methods Isolated rat hearts were exposed to 30 min of global ischaemia followed by 120 min of reperfusion using Langendorff apparatus. Pretreatment with T0901317 (an agonist of LXRs) at various doses (0.1, 0.5 and 1 μmol/L) and ischaemia Myocardial injury was assessed in the terms of infarct size using the triphenyltetrazolium chloride (TTC) staining technique, release of lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes were detected by colorimetry. The following parameters were monitored: LVDP, LVEDP, ± dp/dtmax, coronary flow rat. The relative transcription levels of Glucose transporter 4 (GLUT-4) were quantified by quantitative real-time PCR. The expression of GLUT-4 in myocardial cell membrane was detected by using Western blot.
Results Treatment with T0901317 significantly suppressed ischaemia reperfusion injury induced increases in LDH and CK, also reduced the infarct size conspicuous (P < 0.05). Besides it significantly ameliorated parameters of haemodynamics (P < 0.05). Quantitative real-time PCR analysis showed the GLUT-4 expression was upregulated at mRNA level; Western blot analysis showed the distribution of GLUT-4 in myocardial cell membrane was increased significantly at protein level.
Conclusions Liver X receptor may improve myocardial energy metabolism to reduce ischaemia-reperfusion injury in isolated perfused rat heart by increasing myocardial GLUT4 expression and its distribution in the cell membrane.