大鼠心肺复苏后神经细胞线粒体通透性转换孔的变化

Changes of neural cells mitochondrial permeability transition post cardiopulmonary resuscitation in rats

目的研究大鼠心肺复苏后神经细胞线粒体通透性转换孔(MPTP)的变化规律。方法建立窒息联合冰氯化钾致大鼠心搏骤停、心肺复苏(CA/CPR)的动物模型,断头后提纯大脑皮层组织内线粒体,采用分光光度法测定线粒体MPTP在不同时相的开放程度。结果心肺复苏后大鼠神经细胞线粒体功能明显受损,恢复自主循环(ROSC)后神经细胞MPTP持续处于开放状态,开放程度具有时间依赖性,具体表现为在ROSC后6h以内开放程度保持低水平,6h以后开始迅速大量开放,直至12h开放程度达到最大,但并没有一直维持这一水平,而是在ROSC后24h开放程度略有缩小,表明线粒体开始收缩,至48h开放程度再次加大,72hMPTP明显缩小,但未达到正常水平。结论CA/CPR后大鼠线粒体MPTP出现明显规律性改变,复苏后12h以内可能是改善复苏后脑功能的最佳治疗窗。

Objective To study the changes of mitochondrial permeability transition（ MPT） after cardiac arrest（ CA） and cardiopulmonary resuscitation（CPR）. Methods Sprague Dawley rats cardiac arrest was induced by asphyxiation and ice - cold in 5 min of no circulation. 56 male Sprague Dawley rats were randomly divided into 7 groups： sham control group （ n = 8 ） ; after cardiopulmonary resuscitation the rats were allowed to reperfuse spontaneously for 3,6, 12,24,48,72 h,with each group of 8 rats. The rats were killed by decapitation and the brains were removed, weighed and processed for isolation of mitochondria. Determinations of the mitochondrial permeability transition were based on the absorbance changes of the mitochondrial suspension at 540 nm. Results The opening of mPTP started at 3 h after ROSC, the largest open degree occurred at 12 h,maintained till 72 h after ROSC. Conclusion Regular changes of the opening degree of mitochondrial permeability transition pore were observed after cardiac arrest （ CA ） and cardiopulmonary resuscitation（ CPR） . It is critical to take measure to inhibit the opening of mPTP within 12 h post ROSC.