大鼠神经元线粒体钙单向转运体对线粒体通透性转换孔的调控作用

Calcium uniporter regulates permeability transition pore in brain mitochondria

目的研究离体大鼠神经元线粒体钙单向转运体对线粒体通透性转换孔的调控作用,初步探讨这种调控作用的可能性机制以及在脑保护中的重要意义。方法使用线粒体肿胀法测定线粒体通透性孔的开放程度,分别使用线粒体钙单向转运体抑制剂钌红、激动剂精胺和线粒体通透性转换孔抑制剂环孢菌素处理分离的线粒体,观察吸光度的连续变化。结果与对照组相比,钌红(5μmol/L)使吸光度降低程度与速率明显减小,而精胺(100μmol/L)使吸光度降低的程度与速率进一步增大,但是环孢菌素A(2μmol/L)能够减弱精胺的这种作用。结论在离体大鼠大脑皮层线粒体中,线粒体钙单向转运体可能对线粒体通透性转换孔有调控作用,这种调控机制在脑缺血再灌注脑保护过程中发挥作用。

Objective To determine whether the mitochondrial calcium uniporter plays a role on the mitochondrial permeability transition pore in isolated rat brain mitochondria.Methods Mitochondrial permeability transition pore opening was determined by mitochondrial swelling.Isolated mitochondria were treated with mitochondrial calcium uniporter inhibitor ruthenium red,activator spermine,and mitochondrial permeability transition pore inhibitor cyclosporin A,separately.The continuous change in absorbance was observed.Results Treatment with ruthenium red（5μmol/L）,the extent and rate of decline in the absorbance were attenuated.Spermine（100μmol/L） greatly enhanced the extent and rate of decline,while cyclosporin A（2μmol/L） reversed the effect.Conclusion These results indicate that the mitochondrial calcium uniporter plays a role on the mitochondrial permeability transition pore in isolated rat brain cortex mitochondria.