肝X受体通过调控GLUT-4减轻心肌缺血/再灌注损伤

 目的：探讨肝X受体（LXRs）是否通过调控葡萄糖转运蛋白4（GLUT-4）减轻大鼠离体心脏缺血/再灌注损伤。方法：应用Langendorff装置建立大鼠离体心脏缺血/再灌注损伤模型；实验分组：LXRs激动剂T0901317（0.1 μmol/L、0.5 μmol/L和10 μmol/L）预处理组、缺血预适应组、对照组和模型组；比较各组乳酸脱氢酶（LDH）和肌酸激酶（CK） 活性、心梗面积、左室舒张末压（LVEDP）、左室发展压（LVDP）、左室内压力变化速率（±dp/dt max）、冠脉流量（CF）、心肌组织GLUT-4 mRNA和细胞膜GLUT-4蛋白量。结果：模型组在缺血/再灌注后LDH、CK活性及心梗面积均增加(P<0.05)，并产生血流动力学障碍(P<0.05)；T0901317预处理显著降低CK和LDH活性，减小心梗面积(P<0.05),明显改善因I/R损伤引起的血流动力学障碍 (P<0.05 ),进一步增加由I/R损伤诱导的心肌细胞GLUT-4 mRNA表达及细胞膜GLUT-4蛋白表达(P<0.05)。结论：LXRs可能通过调控GLUT-4表达减轻离体灌流心脏的缺血/再灌注损伤。

Liver X receptors attenuate myocardial ischemia-reperfusion injury through modulating GLUT-4

AIM：To investigate whether liver X receptors (LXRs) attenuate myocardial ischemia-reperfusion (I/R) injury in isolated rat heart through modulating glucose transporter 4 (GLUT-4). METHODS：Isolated rat hearts were used to establish the model of ischemia-reperfusion injury using Langendorff apparatus. The hearts were divided into 7 groups: LXR agonist T0901317 (0.1, 0.5 and 10 μmol/L) pretreatment groups, ischemic preconditioning group, control group, control+DMSO group, and I/R group. The releases of  lactate dehydrogenase (LDH) and creatine kinase (CK), the infarct size, the hemodynamic parameters (left ventricle developed pressure,left ventricle end-diastolic pressure, coronary flow and ±dp/dt max), the relative mRNA level of GLUT-4 and the protein content of GLUT-4 in the myocardial cell membrane were compared between these groups. RESULTS：Besides producing hemodynamic disorders, I/R increased the activities of LDH and CK, and the infarct size in model groups. Treatment with T0901317 significantly suppressed ischemia-reperfusion injury-induced increases in LDH and CK, and reduced the infarct size. T0901317 also significantly ameliorated the parameters of haemodynamics. Treatment with T0901317 significantly increased GLUT-4 expression at mRNA and protein levels in the myocardial cell membrane. CONCLUSION：Liver X receptors may attenuate myocardial ischemia-reperfusion injury in isolated rat heart by modulating the expression of GLUT-4.