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研究生:王霈
研究生(外文):Paul Wang
論文名稱:老化過程中大白鼠不同腦區之氧化壓力的研究
論文名稱(外文):Oxidative stress in the brain of the rat during aging
指導教授:古宏海
指導教授(外文):Ku, Hung-Hai
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:解剖學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:1997
畢業學年度:85
語文別:中文
中文關鍵詞:老化大白鼠氧化壓力
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自由基 (free radical)造成老化的理論認為:生物老化是因為自由基反應引起各種破壞,在體內日積月累的結果。在需氧生物體內產生的超氧陰離子自 由基(superoxide anion,O2-)、氫氧自由基(hydroxyl radical,-OH) 及過氧化氫(hydrogen peroxide,H2O2)等具有高反應能力的含氧自由基,會攻擊脂質、蛋白質及核酸等分子而造成損傷,影響細胞的正常功能。所幸的是,超氧陰離子及過氧化氫的毒害可分別被超氧物歧化酉每(superoxide dismutase,S0D)和過氧化氫酉每(catalase)等抗氧化劑(antioxidant)予以減除。生物體內這種具有傷害性的自由基 (如O2-)與抗氧化劑之間的特定狀態,稱為氧化壓力 (oxidative stress)。細胞內的氧化壓力隨著歲月增強時,就會造成破壞產物的堆積,因而增加突變、腫瘤、疾病甚至死亡的發生率。
根據自由基的老化理論,氧化壓力的程度會隨年齡而增加。腦部被認為是老化過程中最先產生徵兆的所在,同時腦部活動又具有區域性的差異;因此,本研究是想要探討腦部各區域的氧化壓力與年齡之間有怎樣的變化關係。我們利用l、3、6、l2、l8及2l個月齡的雄性Wistar品系大白鼠,分別取出腦部的額葉、頂葉、顳葉、枕葉、次皮質區及小腦後,將部份組織的粒線體分離出來,製成次粒線體物質,以檢測各區腦組織超氧陰離子的產生速率;另外一部份的腦組織磨碎後,分離出細胞質液以檢測細胞內總超氧物歧化酉每、含錳超氧物歧化酉每和過氧化氫酉每活性。實驗結果發現,各腦區超氧陰離子的產生速率隨年齡有增加的趨勢,而總超氧物歧化酉每、含錳超氧物歧化酉每和過氧化氫酉每活性卻在年老時下降,顯示各腦區所遭受的氧化壓力都有隨年齡增加的趨勢;其中次皮質區及小腦在老化過程中表現出較高的超氧陰離子的產生速率,而總超氧物歧化酉每、含錳超氧物歧化酉每和過氧化氫酉每活性在年老時又比其他腦區低,因此次皮質區及小腦所遭受的氧化壓力比其他腦區更為嚴重。本實驗所得結果證實大白鼠腦部六個分區所遭受的氧化壓力有隨年齡增加的情形,對自由基造成老化的理論更多了一項有利的證據。
The free radical theory of aging postulates that free radical reactions cause the progressive accumulation of deleterious changes with age. Free radicals such as 02-, H202 and -OH, formed in biological process of oxidative phosphorylation, can impair lipid, protein and nucleic acids. Notwithstanding, organisms can neutralize, metabolize or subtract the toxic effects by antioxidants, such as superoxide dismutase (SOD) and catalase. Oxidative stress is defined as the balance between production of pro-oxidants and the antioxidant defenses. In the organisms, it is postulated that oxidative stress is a causal factor in the aging process.
On account of its high metabolic rate, brain is reported as the "pacemaker" of process leading to aging. But the regional differences of age-associated changes were lacking.In this proposed study, the brains of male Wistar rats at the ages of 1-, 3-, 6-, 12-, 18- and 21-month were used. Lobes from frontal, parietal, temporal and occipital regions, subcortex and cerebellum were removed separately. The effect of aging on pro-oxidant generation and antioxidant defenses was studied in these brain regions. Pro-oxidant generation was measured as 02- production by submitochondrial particles. Levels of antioxidant defenses were determined by measuring activities of total SOD, Mn-SOD and catalase. The rate of 02- production increased with age in each brain regions. An increasing trend of the activities of total SOD, Mn-SOD and catalase was found during aging from 1-month to 12-month old rats. Then the activities decreased to levels lower than those of 1-month old rats. The most prominent pattern was found both in the subcortex and cerebellum.
In conclusion, oxidative stress may play an important role during aging. The results reveal that the subcortex and cerebellum suffer more oxidative stress than the other regions.



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