线粒体钙单向转运体在心肌低氧/复氧损伤中的作用  

ROLE OF MITOCHONDRIAL CALCIUM UNIPORTER IN MYOCARDIAL HYPOXIA/REOXYGENATION INDUCED INJURY

作　　者：叶挺梅[1] 张世忠[2] 夏强[2] 

机构地区：[1]浙江丽水学院,浙江丽水323000 [2]浙江大学医学院生理学教研室,浙江杭州310031

出　　处：《中国应用生理学杂志》2006年第2期136-140,共5页Chinese Journal of Applied Physiology

基　　金：浙江省科技厅基金资助(2005C30026)

摘　　要：目的:观察线粒体钙单向转运体在心肌低氧/复氧损伤中的作用并探讨其机制。方法:应用Langendorff大鼠心脏灌流模型,低氧/复氧(H/R)采用冠脉前降支结扎30 min、复灌120 min的方法。用生物信号采集系统记录左室发展压(LVDP)、左室压最大上升/下降速率(±dP/dtmax)、左室舒张末压(LVEDP);分光光度法分别检测冠脉流出液中乳酸脱氢酶(LDH)的含量和线粒体活性氧(ROS);TTC染色法检测心肌梗死面积。结果:与单纯低氧/复氧组相比,复氧起始给予线粒体钙单向转运体抑制剂钌红(5μmol/L)明显改善左心室各项功能指标,减小心肌梗死面积,降低线粒体ROS和冠脉流出液中LDH含量;而在复氧期起始给予线粒体钙单向转运体激动剂精胺(20μmol/L),显著升高了线粒体ROS活性,冠脉流出液中LDH含量在复氧5 min、20 min、30 min时显著增多,左心室各项功能指标与心肌梗死面积与单纯低氧/复氧组相比无显著差异。ROS清除剂MPG(1 mmol/L)与精胺联合应用则取消了精胺的作用。结论:抑制线粒体钙单向转运体可能通过减少线粒体ROS的生成减轻心脏低氧/复氧损伤。Aim： To investigate the role and mechanism of mitochondrial calcium uniporter （MCU） in myocardial hypoxia/reoxygenation injury. Methods： Isolated rat hearts were perfused with Langendorff apparatus. The hypoxia/reoxygenation injury was achieved by li gation of left anterior coronary artery for 30 min followed by release of ligation for 120 min. The left ventricular developed pressure （LVDP）. the maximum rise/fall rate of left ventricular pressure （± dP/dtmax）, and the left ventricular end-diastolic pressure （LVEDP） were recorded. Activities of lactate dehydrogenase （LDH） in coronary effluent and reactive oxygen species （ROS） of myocardial mitochondria were spectrophotometrically assayed. Infarct size was determined by TTC staining method. Results： Compared with the hypoxia/reoxygenation （H/R） group, ruthenium red （RR, 5μmol/L）, given at the on set of reoxygenation, significantly improved the contractile function of left ventricle, decreased the myocardial infarct size, alleviated the production of ROS in myocardial mitochondria and LDH release in coronary effluent. Spermine （20μmol/L）, given at the onset of reoxygenation, enhanced the production of ROS in the mitochondria and LDH release in coronary effluent at 5, 20 and 30 min of reoxygenation, however, there were no significant differences of ventricular contractile parameters and infarct size between groups subjected to hypoxia/reoxygenation with or without spermine treatment. Co-treatment of ROS scavenger N-2-mercaptopropionyl glycine （ 1 mmol/L） with spermine abolished the effect of spermine. Conclusion： Inhibition of mitochondrial calcium uniporter may refrain heart from hypoxia/reoxygenation injury via decreasing the production of ROS in heart mitochondria.

关 键 词：心脏 低氧/复氧 线粒体钙单向转运体 活性氧 

分 类 号：R331.3[医药卫生—人体生理学]