記錄
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3613
狀態
NC089FJU00255020
助教
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索書
號
學校
名稱
輔仁大學
系所
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食品營養學系
舊系
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稱
學號
484448028
研究
郭志宏
生(中)
研究
Chih-Hung Guo
生(英)
論文
名稱
(中)
鋁誘發雄性生殖系統毒性之機制
論文
名稱
(英)
The Mechanism of Aluminum-Induced Male Reproductive Toxicity
其他
題名
指導
教授
(中)
王果行
指導
教授
(英)
Guoo-Shyng Wang Hsu
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全文 2004.08.29
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01
學位
類別
博士
畢業
學年
度
89
出版
年
語文
別
英文
關鍵
鋁 一氧化氮合成酶 生精作用 睪固酮 炎症反應 氧化壓力
字(中)
關鍵 Aluminum Nitric oxide synthase Spermatogenesis Testosterone Inflammatory
字(英) reaction Oxidative stress
摘要
(中)
因高鋁誘發雄性生殖系統毒性之機制仍不清楚。本論文就氯化鋁對 雄性
生殖毒性作深入探討。以腹腔注射給予 CD-1 雄性小白鼠不同劑量之氯
化鋁 (2 週)，分成對照組 (0 mg Al/kg/day)、低鋁 (7 mg Al/kg/day)、中鋁
(13 mg Al/kg/day)、及高鋁 (35 mg Al/kg/ day) 四組。結果發現鋁毒性可能
直接作用在睪丸組織。在低鋁組並未發現毒性作用，但中鋁及高鋁組之
生精 (spermatogenesis)、固醇生成作用 (steroidogenesis)、與生殖表現則明
顯較對照組差。鋁聚積在睪丸組織明顯誘發相對組織位置的誘發型一氧
化氮合成酶 (inducible nitric oxide synthase, iNOS) 之蛋白及 mRNA 表現，
過量的一氧化氮產物 (NO) 與睪固酮 (testosterone) 濃度呈明顯之負相關
性。混合投予高鋁與 iNOS 抑制劑 (L-NIL, 20 mg/kg/day, 12 days) 組其睪
丸組織的 NO 產物較單獨投予高鋁組為低，然而睪固酮濃度明顯較高。
顯示鋁誘發 iNOS 產生過量之 NO，造成睪固酮的合成分泌明顯被抑制。
然而，鋁誘發 NO 形成亦與炎症反應 (inflammatory reaction) 有關。高鋁
組睪丸組織有較低的 cyclic AMP、及膽固醇支鏈裂解酶(cholesterol sidechain cleavage enzyme, p-450scc)、與較高的膽固醇含量，推測因鋁誘發
NO 產物抑制 cyclic AMP，使得較少的膽固醇進入粒腺體，並抑制 p450scc 使得膽固醇無法進一步裂解。此外，過高的 NO 可以增加鋁對於
膜的通透性，造成組織內聚積較高的鋁濃度。本論文亦發現，睪丸組織
有較低的鋅、與較高的鐵及銅離子，組織的脂質過氧化指標
(thiobarbituric acid-reactive substances, TBARS) 顯著較高。建議高鋁環境改
變睪丸組織的離子代謝並增加氧化壓力。
摘要
(英)
論文
目次
The precise mechanisms of aluminum (Al)-induced male reproductive toxicity
remain to be elucidated. The present investigations have been conducted on the
reproductive toxicity in adult males exposed to Al. Al chloride was intraperitoneal
administered to male mouse at doses of 0, 7, 13, and 35 mg Al/kg/day for 2 weeks
(designated as C, LAL, MAL and HAL) respectively. The results suggested that
Al exerted its toxic effect directly at the testis rather than hypothalamus-pituitary.
Significantly detrimental effects on spermato- genesis, steroidogenesis and
reproductive performance were found at LAL and HAL groups. The induction of
inducible nitric oxide synthase (iNOS) protein over-expression and -transcription
in testis was corresponded to Al accumulation. Increasing production of NO,
induced by accumulated Al, was negative correlated to testosterone levels.
Administrating Al with iNOS inhibitor (L-NIL, 20 mg/kg/day) for a period of 12
days, decreased the NO products and elevated testosterone levels. This result
confirmed that Al depressed testosterone through inducing NO production.
However, an inflammatory reaction might be involved in Al-induced excessive
NO products. The results of decreased cyclic AMP and interfered the activation of
cholesterol side-chain cleavage enzyme (p-450scc) implicated that Al might
decrease the across of cholesterol through mitochondrial membrane by Al
accumulation in testis. In addition, excessive NO increased the permeability of
organism membrane for Al, possibly involved in more Al accumulation. The
present study also showed that high level of Al resulted in lower zinc and higher
iron, copper and TBARS (thiobarbituric acid-reactive substances) levels in the
testis of mice. It was suggested that the Al intoxication associated with the
occurrence of abnormal mineral metabolism and increasing oxidative stress in the
testes of mice.
中文摘要Ⅰ 英文摘要Ⅱ 第一章 緒論 1 第二章 文獻回顧 2 壹、鋁 1.1. 鋁
之特性 3 1.2. 鋁毒性之臨床特徵 4 1.3. 影響鋁吸收之因素 6 1.4. 鋁毒性與
貧血 7 1.5. 鋁毒性對神經細胞或神經發育的影響 9 1.6. 鋁對動物母體及其
子代發育之毒性 11 1.7. 鋁對於雄性生殖系統之毒性 14 1.8. 鋁毒性之可能
機制 15 貳、一氧化氮 2.1. 一氧化氮合成酶之特性 19 2.2. 一氧化氮與脂
質過氧化之發生 22 2.3. 一氧化氮對母體及子代之毒性作用 24 2.4. 一氧化
氮對雄性生殖系統之毒性作用 25 一氧化氮引起精細胞死亡 25 一氧化氮
抑制雄性激素的合成與分泌 26 一氧化氮抑制類脂醇生合成酵素之表現
27 一氧化氮抑制腦下腺的激素分泌 28 2.5. 一氧化氮與貧血 29 一氧化氮
誘發血基質的瓦解 30 一氧化氮降低鐵蛋白的鍵結能力 30 一氧化氮改變
參與血紅素生成酵素之活性 32 第三章 探討之問題與進行之方向 34 第四
章 鋁誘發雄性小白鼠生殖系統之毒性 中文摘要 36 英文摘要 37 前言 38
材料與方法 38 結果 41 討論 42 圖表 44 第五章 鋁誘發睪丸組織的一氧化
氮產物及降低睪固酮濃度 中文摘要 49 英文摘要 50 前言 51 材料與方法
51 結果 52 討論 53 圖表 57 第六章 鋁聚積在睪丸組織與誘發一氧化氮合
成酶表現 中文摘要 61 英文摘要 62 前言 63 材料與方法 63 結果 72 討論
74 圖表 76 第七章 鋁誘發一氧化氮產物抑制睪丸組織的固醇生成作用 中
文摘要 81 英文摘要 82 前言 83 材料與方法 83 結果 85 討論 86 圖表 89
第
八章 鋁毒性致睪丸組織產生發炎反應及抑制睪固酮濃度 中文摘要 93 英
文摘要 94 前言 95 材料與方法 95 結果 97 討論 97 圖表 99 第九章 鋁毒性
改變睪丸組織的離子分佈與誘發氧化壓力 中文摘要 103 英文摘要 104 前
言 105 材料與方法 105 結果 106 討論 107 圖表 110 第十章 參考文獻 114
第十一章
156
Abdulla, M.,著作發表
Svensson, S.,
Haeger-Aronson, B., 1979. Antagonistic effects of zinc
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