- 學位論文
花生四烯酸於幼鼠小腦顆粒細胞造成細胞凋亡機制之探討
The Mechanism of Arachidonic Acid Induced Apoptosis in Rat Cerebellar Granule Cells
摘要
摘 要 腦組織缺血(或缺氧)及再灌流傷害(ischemia-reperfusion injury)常發生於腦中風，癲癇經攣，以及神經退化性疾病。腦組織缺血再灌流後，會造成腦細胞的能源供應產生障礙，影響鈣離子恆定，大量釋出花生四烯酸，產生氧自由基、一氧化氮、以及活化多種激脢及前列腺素，因而導致神經細胞的死亡。而其中Arachidonic acid (AA；花生四烯酸)對於細胞的生理功能更是有著相當廣泛的影響。神經細胞的死亡可以分為兩類，凋亡 (apoptosis) 以及壞死 (necrosis) ，本研究特別探討凋亡的部份。引起凋亡的路徑當中，其中一條重要的路徑是與粒線體有關的，開始於在膜間隙中的一些蛋白質，包括cytochrome c(cyt-c)，經由粒線體雙層膜上之滲透轉換孔道(permeation transition pore)打開而釋出，接著活化一連串下游 caspase 的反應，而導致 chromatin 的濃縮和 DNA 的斷裂。然而，由於缺血性傷害而導致 AA 大量產生與 apoptosis 之間的關係，至今尚未有一明確的答案。在本篇研究中，我們給予AA (10
並列摘要
Abstract The ischemic injury is associated with severe cellular injury in stroke, seizure, Alzheimer’s disease and many other degenerative disorders of nervous system. Reperfusion after brain ischemia results in disorder of energy supply, the perturbation of calcium homeostasis, the production of arachidonic acid; oxyradicals and nitric oxide, and activation of many kinases and prostaglandins of nervous system, leading to the death of nervous cell. Arachidonic acid (AA) and its metabolites have been shown to have important physiological or patho-physiological functions in nervous system. The death of neurons can be divided into two categories: apoptosis and necrosis. In the present study, we especially focus on the apoptosis. Of many pathways inducing apoptosis, one of them is related to mitochondria. This pathway initiates at the release of cytochrome c from the mitochondrial permeation transition pore, then cytochrome c triggers the activation of caspases cascade, resulting in the condensation of chromatin and fragmentation of DNA. However, the relationship between AA abundantly produced and apoptosis during ischemia injury is still unclear. In the present study, we applied AA (10