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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
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)
关键词
肝X受体
心肌缺血
再灌注损伤
葡萄糖转运蛋白4
Liver X receptors
Myocardial ischemia
Reperfusion injury
Glucose transporter 4