| 研究生: |
鄒博成 Tzou, Bo-Cheng |
|---|---|
| 論文名稱: |
探討重金屬鎘誘發星狀膠細胞氧化傷害及鞣花酸抑制鎘導致的氧化傷害之機轉 Studies on cadmium-induced astrocytic oxidative injury and antioxidative effect of ellagic acid on cadmium-treated astrocytes |
| 指導教授: |
曾淑芬
Tzeng, Shun-Fen |
| 學位類別: |
碩士 Master |
| 系所名稱: |
生物科學與科技學院 - 生命科學系 Department of Life Sciences |
| 論文出版年: | 2006 |
| 畢業學年度: | 94 |
| 語文別: | 中文 |
| 論文頁數: | 72 |
| 中文關鍵詞: | 鎘 、星狀膠質細胞 、小膠質細胞 、氧化壓力 、神經細胞 |
| 外文關鍵詞: | astrocyte, microglia, neuron, oxidative stress, cadmium |
| 相關次數: | 點閱:78 下載:2 |
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隨著全球工業化發展,越來越多的重金屬鎘被排放到環境中。最近許多研究指出長期暴露在高濃度鎘環境將產生神經毒性,並且可能與許多慢性中樞神經疾病有所關連。星狀膠質細胞為中樞神經系統中主要的膠質細胞,在神經細胞的成熟、滋養神經細胞、微環境中離子的平衡,以及神經傳導物質的清除等扮演主要的角色。本實驗以20 μM氯化鎘處理初級星狀膠質細胞24小時後,細胞形態萎縮且細胞活性顯著下降。進一步觀察胞內鈣離子濃度,發現處理30 μM氯化鎘後,胞內鈣離子濃度顯著增加,推測鎘離子可能干擾鈣離子平衡,使胞內鈣離子濃度快速增加而導致細胞死亡。接著使用胞內與包外鈣離子螯合劑預先處理細胞能顯著降低鎘所造成之細胞死亡。我們亦觀察細胞經過鎘處理後,胞內活性氧化族群有增加的趨勢,粒腺體膜功能亦受到影響。再同時處理天然抗氧化物鞣花酸之後,能有效降低胞內氧化壓力以及細胞死亡。此外亦發現鎘會干擾胞內超氧化歧異脢之活性,且持續表現鋅銅超氧化歧異脢能降低鎘所造成之胞死亡。綜合上述,我們推測鎘可能藉由引起胞內鈣離子過量增加、降低超氧化歧異脢活性,使得粒腺體功能受損並增加胞內氧化壓力,最後造成細胞死亡。
Cadmium (Cd), a heavy metal generally used in modern industry, has been reported to induce neurotoxicity, and Cd-inudced injury is thought to be associated with CNS neurodegenerative disorders. Astrocytes a major CNS glia, play a supportive role in neuronal maturation, neuroprotection and neurotransmission. In this study, we found that treatment of astrocytes with CdCl2 at the concentrations greater than 20 μM for 24 h resulted in the dystrophy of astrocytes. Examination of intracellular calcium levels [Ca2+]i indicated that treatment of CdCl2 at 30 μM rapidly induced an increase in [Ca2+]i, suggesting that Cd-induced astrocytic death may be resulted from the disturbance of homeostasis of [Ca2+]i via rapidly Ca2+ influx. Indeed, pretreatment of EGTA and BAPTA prevented astrocytic cell death from Cd insult. We also found that the level of free radicals in astrocytes were increased following Cd treatment. Moreover, pretreatment with 30 µM of antioxidant ellagic acid and overexpression of Zn,Cu-SOD inhibited Cd-induced astrocytic cell death. We demonstrate here that Cd induces astrocytes toward programmed cell death, which may be due to the overload of [Ca2+]i, interruption of SOD and increase of oxidative stress, then subsequently triggering mitochondrial dysfunction. Our study suggests that Cd promotes neuronal cell death via inducing astrocytic cell death.
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