Nakahara I
Department of Neurosurgery, Faculty of Medicine, Kyoto University.
Nihon Geka Hokan. 1990 Jan 1;59(1):27-38.
Changes of brain mitochondrial phospholipids during cerebral ischemia and recirculation were experimentally studied in a rat 4-vessel occlusion model, to explore the relation between changes of mitochondrial phospholipids and dysfunction of mitochondria. Respiratory functions, activities of respiratory enzymes (cytochrome c oxidase, F0F1-ATPase) were analyzed after 30 and 60 minutes of ischemia, and after 30 minutes of recirculation following each ischemic period. Activities of respiratory functions and respiratory enzymes decreased progressively during ischemia, which recovered completely after recirculation following 30 minutes of ischemia, while only partial recovery was observed after recirculation following 60 minutes of ischemia. In phospholipid analyses, contents of phospholipid classes tended to decrease time-dependently during ischemia, and compositions of polyunsaturated fatty acids (PUFA) such as arachidonic acid (20:4) and docosahexaenoic acid (22:6) were decreased preferentially. In recirculation, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) showed recovery of contents of phospholipids and compositions of PUFA after recirculation following 30 minutes of ischemia, while further decrease of contents of phospholipids and compositions of PUFA were observed after recirculation following 60 minutes of ischemia, especially in CL. On the other hand, progressive degradation of phospholipids occurred after recirculation following both 30 and 60 minutes of ischemia in phosphatidylserine and phosphatidylinositol. Changes of major phospholipid classes such as PC, PE, and CL correlated with the changes of mitochondrial respiratory functions and activities of respiratory enzymes. In conclusion, changes of mitochondrial membrane phospholipids appear to affect the integrity of cellular energy metabolism via mitochondrial dysfunction during cerebral ischemia and recirculation.
在大鼠四血管闭塞模型中,通过实验研究了脑缺血及再灌注过程中脑线粒体磷脂的变化,以探讨线粒体磷脂变化与线粒体功能障碍之间的关系。在缺血30分钟和60分钟后,以及每个缺血期后的再灌注30分钟后,分析呼吸功能、呼吸酶(细胞色素c氧化酶、F0F1 - ATP酶)的活性。在缺血过程中,呼吸功能和呼吸酶的活性逐渐下降,缺血30分钟后的再灌注后完全恢复,而缺血60分钟后的再灌注后仅观察到部分恢复。在磷脂分析中,磷脂类含量在缺血过程中呈时间依赖性下降,花生四烯酸(20:4)和二十二碳六烯酸(22:6)等多不饱和脂肪酸(PUFA)的组成优先下降。在再灌注时,缺血30分钟后的再灌注后,磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)和心磷脂(CL)的磷脂含量和PUFA组成恢复,而缺血60分钟后的再灌注后,观察到磷脂含量和PUFA组成进一步下降,尤其是CL。另一方面,缺血30分钟和60分钟后的再灌注后,磷脂酰丝氨酸和磷脂酰肌醇中的磷脂逐渐降解。PC、PE和CL等主要磷脂类的变化与线粒体呼吸功能和呼吸酶活性的变化相关。总之,线粒体膜磷脂的变化似乎在脑缺血及再灌注过程中通过线粒体功能障碍影响细胞能量代谢的完整性。