Gao Qin, Zhang Shi-zhong, Mao Huan-hao, Li Qing-song, Cao Chun-mei, Xia Qiang
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2006 Aug;22(3):278-82.
To investigate whether mitochondrial calcium uniporter participates in the cardioprotection of tumor necrosis factor alpha (TNFalpha) pretreatment in isolated rat hearts subjected to ischemia/reperfusion.
Isolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, coronary flow (CF) and lactate dehydrogenase (LDH) release during reperfusion were measured. The mitochondria of the heart were isolated and suspended in the swelling buffer for measurement of absorbance at 520 nm.
Pretreatment with TNFa at 10 U/ml for 7 min followed by 10 min washout reduced the infarct size and LDH release, and improved the recovery of CF during reperfusion. Administration of spermine (20 micromol/L), an opener of mitochondrial calcium uniporter, for 10 min during early reperfusion attenuated the reduction of infarct size and LDH release, and improvement of CF induced by TNFalpha. In isolated mitochondria of the heart pretreated with TNFalpha, the absorbance at 520 nm decreased less than that of mitochondria without TNFalpha pretreatment. Administration of spermine (50 micromol/L) attenuated the change of the absorbance induced by TNFalpha.
The findings indicate that TNFalpha protects myocardium against ischemia/reperfusion injury via inhibiting mitochondrial calcium uniporter opening as well as mitochondrial permeability transition pore opening.
研究线粒体钙单向转运体是否参与肿瘤坏死因子α（TNFα）预处理对离体大鼠心脏缺血/再灌注的心脏保护作用。
将离体灌注的大鼠心脏进行30分钟的局部缺血（左冠状动脉前降支闭塞）和120分钟的再灌注。测量再灌注期间的梗死面积、冠状动脉血流量（CF）和乳酸脱氢酶（LDH）释放。分离心脏线粒体并悬浮于肿胀缓冲液中，测量520nm处的吸光度。
用10U/ml的TNFα预处理7分钟，随后冲洗10分钟，可减小梗死面积和LDH释放，并改善再灌注期间CF的恢复。在再灌注早期给予线粒体钙单向转运体开放剂精胺（20μmol/L）10分钟，可减弱TNFα诱导的梗死面积减小和LDH释放减少以及CF改善。在经TNFα预处理的心脏离体线粒体中，520nm处的吸光度下降幅度小于未用TNFα预处理的线粒体。给予精胺（50μmol/L）可减弱TNFα诱导的吸光度变化。
研究结果表明，TNFα通过抑制线粒体钙单向转运体开放以及线粒体通透性转换孔开放来保护心肌免受缺血/再灌注损伤。
