肝X受体通过调控GLUT-4减轻心肌缺血/再灌注损伤  

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

作　　者：郑耀富 殷然[1] 王梦洪[1] 郑泽琪[1] 彭景添[1] 

机构地区：[1]南昌大学第一附属医院心血管内科,江西省高血压研究所,江西南昌330006

出　　处：《中国病理生理杂志》2014年第1期18-24,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81000071)

摘　　要：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(0.1μmol/L、0.5μmol/L和1.0μmol/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。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 ttmol/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 hemedynamic parameters （left ventricle developed pressure,left ventricle end-diastolic pressure, coro- nary flow and ~ dp/dtm~）, 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 I＇0901317 significantly suppressed is- chemia-reperfusion injury-induced increases in LDH and CK, and reduced the infarct size. T0901317 also significandy a- meliorated the parameters of haemodynamics. Treatment with T0901317 significantly increased GLUT-4 expression at mR- NA and protein levels in the myocardial cell membrane. CONCLUSION： Liver X receptors may attenuate myocardial is- chemia-reperfusion injury in isolated rat heart by modulating the expression of GLUT-4.

关 键 词：肝X受体 心肌缺血 再灌注损伤 葡萄糖转运蛋白4 

分 类 号：R363[医药卫生—病理学]