摘要
目的:观察线粒体钙单向转运体在低氧预处理心肌保护中的作用及其与线粒体通透性转换孔之间的关系。方法:采用Langendorff灌流离体大鼠心脏模型,记录左室发展压(LVDP)、左室压上升/下降最大速率(±dp/dtmax)和左室舒张末期压力(LVEDP)。结扎冠脉左前降支30min作为低氧,松开结扎复氧120min。全心停灌5min复氧5min两个循环作为低氧预处理。用紫外分光光度法检测复氧5、10、15、20和30min的冠脉流出液乳酸脱氢酶(LDH)活性。用TTC染色法测心肌梗死面积。结果:低氧预处理和低氧后复氧期的前10min用钌红(5μmol/L)处理均可促进LVDP、±dp/dtmax和LVEDP的恢复,减小心肌梗死面积,减少LDH释放。复氧期的前10min用精胺(20μmol/L)处理可减弱低氧预处理的心脏作用。用环孢菌素A(0·2μmol/L)处理20min(复氧前5min到复氧期的前15min)则减弱上述精胺在低氧预处理中的心肌作用。结论:低氧预处理引起的心肌保护机制可能涉及线粒体钙单向转运体活动及其线粒体通透性转换孔开放的抑制。
AIM： To investigate the role of mitochondrial calcium uniporter （MCU） in the cardioprotection by hypoxic preconditioning （HPC） and its relationship to mitoehondrial permeability transition pore （MPTP）. METHODS： Intraventricular balloon technique was employed to measure the left ventrieular developed pressure （ LVDP）, the maximum rise/fall rate of left ventrieular pressure （ ± dp/dtmax）, and the left ventrieular end - diastolic pressure （LVEDP） in Langendorff isolated rat heart. The hypoxia was achieved by ligation of left anterior coronary artery for 30 min followed by release of ligation for 120 min as reoxygenation. Hypoxie preconditioning was set as two episodes of 5 min global hypoxia and 5 min reoxygenation. RESULTS： Both HPC and treatment with ruthenium red （5 μmol/L） during the first 10 min reoxygenation improved recovery of LVDP ± dp/dtmax and decreased LVEDP, which was associated with reduced infarct size and lactate dyhydrogenase release. These protective effects were at- tenuated by treatment with spermine （20 μmol/L） during the first 10 min reoxygenation. Administration of cyclosporin A （0.2 μmol/L） during the last 5 min of hypoxia period and first 15 min of reoxygenation period reduced the injury effect by spermine. CONCLUSION： These results indicate that inhibition of MCU is involved in the cardioprotection of HPC via inhibiting MPTP.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2006年第2期279-283,共5页
Chinese Journal of Pathophysiology
基金
浙江省自然科学基金青年人才专项资金资助(No.RC99038)
浙江省科技厅资助项目(2005C30026)
关键词
心脏
缺氧预处理
线粒体钙转运体
线粒体通透性转换孔
Heart
Hypoxic preconditioning
Mitochondrial calcium uniporter
Mitochondrial permeability transition pore
