探討視網膜神經細胞對鎘的毒性反應

在高度工業發展的環境下，產生不少的重金屬鎘 (Cd : Cadmium) 被排放到生活的環境當中，鎘也被認定是環境和工業污染當中的有毒物質，經由細胞氧化壓力所產生的傷害導致各種自由基的產生，體內的自由基無法正常代謝，最後細胞內累積的氧化壓力產生細胞毒，使得細胞的染色體產生突變，喪失生理功能或最後走向死亡。許多的研究指出鎘會造成神經毒性，並且和中樞神經系統中一些神經退化性疾病有關聯。有文獻指出鎘在細胞內會產生大量活性氧 (ROS :reactive oxygen species)，引起粒線體中膜電位下降，cytochrome c釋放，造成Apaf-1、caspase9和caspase3一連串的活化作用，進而讓細胞死亡。本研究對於眼球內部對於重金屬殘留所造成的影響，及視網膜神經細胞對於鎘導致的氧化壓力所產生的細胞毒性反應，以Neuro-2a細胞來探討存活度及凋亡路徑。利用N-acetylcysteine (NAC)， SB203580，U0126，SP600125等casepase抑制劑來觀察鎘誘發的細胞毒性及細胞凋亡現象是否有被抑制的現象，並藉由NAC，做為ROS的抑制劑，證明Neuro-2a細胞是受到ROS的影響而導致細胞的死亡。在本研究有助於瞭解鎘誘發Neuro-2a細胞ROS藉由caspase路徑導致細胞凋亡的現象。

In the height of industrial development environment, resulting in a lot of heavy metal cadmium (Cd) released into the environment are among the living, cadmium has also been identified among environmental and industrial pollution of toxic substances, resulting in a variety of cell damage by free radicals produced by oxidative stress, free radicals can not be normal metabolism, the final cumulative oxidative stress cell cytotoxic, it allows cells to produce chromosomal mutation, loss of physiological functions or the last to die. Many studies indicate cadmium can cause neurotoxicity, and some of the central nervous system and neurodegenerative disorders are associated. Documented that the cadmium in the cell will produce large amounts of reactive oxygen species (ROS : reactive oxygen species), cause mitochondrial membrane potential drop, cytochrome c release, cause Apaf-1, caspase 9 and caspase 3 activation series, thereby allowing cell death. In this study, the impact inside the eye caused by heavy metal residues, and the cytotoxic response of retinal neurons to oxidative stress caused by cadmium generated, to explore the viability and apoptotic pathways using Neuro-2a cells. The use of N-acetylcysteine (NAC), SB203580, U0126, SP600125 and other casepase inhibitor to observe the cadmium-induced cytotoxicity and apoptosis in whether there is suppressed phenomenon, and by the NAC, as an inhibitor of ROS, Neuro-2a cells is proved by the impact of ROS leading to cell death. In this study help to understand the Neuro-2a cells induced by cadmium ROS by caspase path leading to apoptosis phenomenon.