臺灣博碩士論文加值系統

輔仁大學八十七年度第二學期碩士論文摘要
系（所）別：食品營養學系碩士班 研究生：鄒素珍
論文名稱：探討長期低硒攝取-再補充期間維生素E不足對大白鼠含硒蛋白質與氧化傷害指標之影響
指導教授：駱菲莉 博士
摘 要
本研究的目的在給予大白鼠8或16週低硒攝取過程中，同時配合給予低維生素E飼料以期提高氧化壓力，之後再補充硒0.2 mg/kg diet為期2週，以評估此實驗模式對大白鼠各臟器中phospholipid-hydroperoxide glutathione peroxidase (phGPX)、cellular glutathione peroxidase (cGPX)、extracellular glutathione peroxidase (eGPX)等含硒蛋白質及對各臟器的TBARS、protein carbonyls、thiols、glutamine synthetase (GS)、gluose-6-phosphate dehydrogenase (G-6PD)及血漿lactate dehydrogenase (LDH)等過氧化傷害指標的影響。
分析飼料成分後得知，在低硒攝取期中，飼料的硒含量約為0.05 mg Se/kg diet，為大白鼠正常需求0.1 mg Se/kg diet的50 %，不如預期低。維生素E足量飼料的維生素E含量為253 mg α- tocopherol/kg diet；維生素E缺乏飼料的維生素E含量為33 mg α- tocopherol/kg diet，後者僅略低於大白鼠的維生素E正常需求。
在低硒攝取期內，睪丸的cGPX活性及硒含量均無顯著下降。心臟硒含量在低硒攝取8週時即降為控制組的50 %，但phGPX及cGPX活性卻分別顯著增加至控制組的186 %與133 %，再於低硒攝取16週時分別下降至控制組的49 %與54 %。低硒攝取期間肝臟的cGPX活性的降幅最大，低硒攝取8週時降至控制組的40 %。其餘臟器及紅血球的cGPX活性與硒含量均在低硒攝取8週時即顯著降低，但phGPX活性則均在低硒攝取16週時才見顯著降低。血漿eGPX活性在低硒攝取8週時降至控制組的50 %，但血漿硒含量卻已經降至控制組的15 %。在肝臟、心臟、肺臟及睪丸的內生性、激發性TBARS及TBARS激發倍數均是低硒攝取16週組顯著高於低硒攝取8週組；但腎臟的內生性、激發性TBARS及TBARS激發倍數是低硒攝取16週組顯著低於低硒攝取8週組。由低硒攝取期間的protein carbonyls、thiols、GS及G-6PD活性變化指出，在各臟器均出現程度不一的蛋白質過氧化傷害，以心臟及肝臟受損最大。在低硒攝取時，肝臟維生素E含量的降幅最大。而肺臟及心臟之維生素E含量則在低硒攝取8週時上升，而後於低硒攝取16週下降至與控制組相仿，變化趨勢雷同於心臟的phGPX及cGPX活性。在低硒攝取期內，紅血球維生素E足量組的phGPX活性保留率顯著高於維生素E缺乏組。
在硒補充期間，各臟器的phGPX及cGPX活性均顯著回升，至硒補充2週時，各臟器的phGPX活性可回升至控制組的90~140 %，但各臟器的cGPX活性則僅約回升至控制組的75~95 %。而各臟器的硒含量回復情形亦相似於cGPX活性變化。至硒補充2週時，紅血球phGPX及cGPX活性分別回升至控制組的96 %與67 %，但紅血球硒含量卻只回復至控制組的57 %；而血漿eGPX活性與硒含量則均回升至控制組的85 %左右。肺臟及心臟TBARS激發倍數在硒補充期內均未見顯著增加，但肝臟、腎臟及睪丸的維生素E缺乏組TBARS激發倍數則仍隨硒補充時間增加而上升，且顯著高於維生素E足量組。在硒補充期內，各臟器的各項蛋白質過氧化損傷指摽均獲得改善；肝臟的維生素E含量會顯著回升，但未達與控制組相仿的程度；心臟的維生素E含量可在硒補充1天時即回升至高於控制組的程度。在硒補充期內，腎臟及紅血球維生素E足量組的phGPX活性及腎臟的cGPX活性回升率顯著高於維生素E缺乏組。
在硒耗竭期內，估計的血漿Se-P含量顯著降低至約為控制組的15 %；但在硒補充期的3天內血漿Se-P含量迅速回升。
總言在本硒耗竭-再補充且維生素E攝取不足的研究模式下，各臟器phGPX活性衰退較慢且回升較快，可能顯示phGPX在大白鼠的生理重要性高於cGPX，尤其是心臟及睪丸。可能因為各臟器的生理保護機轉不同，導致蛋白質過氧化傷害程度不一。血漿Se-P含量變化可能為較佳的反映短期硒營養狀況指標。

Effects of Long Term Inadequate Selenium and Vitamin E Consumption and Selenium Repletion on Selenoproteins and Indices of Oxidative Damage of Rats
Su-Chen Tsou
Abstract
The purposes of this study were to evaluate the pattern of changes in selenoproteins including phospholipid-hydroperoxide glutathione peroxidase (phGPX), cellular glutathione peroxidase (cGPX) and extracellular glutathione peroxidase (eGPX) and indices of oxidative protein damage including protein carbonyls and thiols contents, tissue activities of glutamine synthetase (GS), glucose-6-phosphate dehydrogenase (G-6-PD) and plasma lactate dehydrogenase (LDH) in rats by using a long-term inadequate selenium and vitamin E consumption and selenium repletion study model.
The results showed that selenium content the of inadequate selenium diet was 0.05 mg/kg diet, equivalent to 50 % of the selenium requirement. Vitamin E contents of vitamin E adequate and inadequate diet were 253 and 33 mg α-tocopherol/kg diet, respectively. Vitamin E level of the vitamin E inadequate diet was 55 % lower than vitamin E requirement of rats.
There were no significant decrease in testis cGPX activity and selenium content during inadequate selenium consumption. After 8 weeks of selenium inadequacy, heart selenium content fell to 50 % of control, whereas phGPX and cGPX activities of heart increased to 186 % and 133 % of control, then fell to 49 % and 54 % of control after 16 Se weeks of inadequacy. Among all organs, liver had the greatest fall of liver cGPX activity. The cGPX activities and selenium contents of other tissues and erythrocytes decreased significantly after 8 weeks of inadequate Se intake, but phGPX activities did not significantly decrease until 16 weeks of inadequate Se consumption. After 8 weeks of inadequate selenium intake, plasma eGPX activity fell to 50 % of control, but plasma selenium content dropped to 15 % of control. The endogenous TBARS, Fe2+-stimulated TBARS and TBARS stimulation of liver, heart, lung and testis were higher after 16 weeks of Se inadequacy than after 8 weeks, whereas the opposite result appeared in kidney. The tissue levels of protein carbonyls and thiols content, GS, G-6-PD and LDH activities during inadequate selenium consumption showed various degree of oxidative protein damage, especially in heart and liver. During inadequate selenium consumption, liver had the greatest fall in its vitamin E among all tissues. The vitamin E contents of heart and lung were higher than control after 8 weeks of inadequate selenium intake, then return to the similar level of control after 16 weeks of Se inadequacy. Animals of vitamin E adequate group maintained greater erythrocyte phGPX activity than vitamin E inadequate animals did during inadequate selenium consumption.
After 2 weeks of selenium repletion, phGPX activities of all tissues returned to 90~140 % of control, but cGPX activities of all tissues returned only to 75~95 % of control. The changes in tissues selenium contents during selenium repletion were similar to cGPX activities. The phGPX and cGPX activities of erythrocyte returned to 96 and 67 % of control after 2 weeks of repletion, while erythrocyte selenium content returned only to 57 % of control. In addition, plasma selenium content and eGPX activity returned to 85 % of control after the 2-week repletion. During selenium repletion, TBARS stimulation of lung and heart did not change significantly, but TBARS stimulation of liver, kidney and testis in vitamin E inadequate groups still increased with selenium repletion. The indices of protein oxidation damage showed gradual improvement during selenium repletion. The vitamin E content of liver gradually increased to a level slightly lower than control during selenium repletion. Meanwhile the resumption of kidney and erythrocyte phGPX activities and kidney cGPX activity of vitamin E adequate groups were higher than that of vitamin E inadequate groups.
During selenium inadequacy, the estimated Se-P level fell to 15 % of control, and dramatically returned after 3 days of selenium repletion.
In summary, the greater degree of resumption in tissues phGPX activity than cGPX activity during selenium repletion, suggested greater tissues needs for phGPX than for cGPX after 16 weeks of inadequate selenium consumption, especially in heart and testis. Among all selenoproteins studied, plasma Se-P level seemed very suitable for evaluating recent changes in dietary selenium intake for its parallel changes with feed selenium level during the entire study model.

目 錄
第一章 前言……………………………………………………………………....... 1
第二章 文獻回顧………………………………………………………… 2
一、硒的簡介……………………………………………………………… 2
二、各含硒蛋白質的簡介………………………………………………… 2
1. SeGPX……………………………………………………………...... 3
2. phGPX……………………………….……………………………..... 3
3. Se-P………………………………………………………………... 4
4. Iodothyronine 5’-deiodinases………………………………… 5
5. 其他…………………………………………………….…………. 5
三、硒對人體及動物健康之影響………………………………………… 6
1. 硒缺乏……………………………………………………………. 6
2. 硒的毒性…………………………………………………………. 7
四、GPX的抗氧化作用………………………………………………….. 8
五、飲食中硒含量對phGPX的影響………………………….…………. 10
六、phGPX和維生素E的交互作用…………………………………….. 11
七、高氧化壓力對動物組織之傷害……………………………………… 14
八、研究目的與假說……………………………………………………… 15
第三章 材料與方法………………………………………………………. 16
一、實驗設計……………………………………………………………… 16
二、動物飼養環境………………………………………………………… 17
三、飼料配製……………………………………………………………… 17
四、動物犧牲程序及樣本收集…………………………………………… 18
五、分析項目……………………………………………………………. 19
1. 組織中含硒蛋白質之分析………………………………………. 19
(1) 組織中phGPX, cGPX及eGPX之酵素活性………………… 19
(2) Se-P……………………………………………….………….. 19
2. 各組織之病理切片………………………………………………. 20
3. 各組織中氧化傷害之生化指標…………………………………. 20
(1) TBARS含量………………………………………………… 20
(2) Protein carbonyls…………………………………………….. 20
(3) Protein thiols……………………………………..…………... 21
(4) GS……………………………………………………………. 21
(5) G-6PD…………………………………………...…………… 21
(6) LDH………………………………………………………….. 22
4. 其他參考資料……………………………………………………. 22
(1) 飼料與組織硒含量…………………………………………. 22
(2) 飼料與組織中維生素E含量………………………………. 22
(3) 蛋白質分析…………………………………………………. 22
六、統計方法……………………………………………………………… 23
第四章 結果…………………………… ………………………………… 24
一、 飼料中的硒及維生素E含量……………………………………….. 24
1. 飼料中硒含量……………………………………………………. 24
2. 飼料中維生素E含量……………………………………………. 24
二、 動物的觀察及體重變化………………………………………….. 25
三、 各含硒蛋白質的變化…………………………………………….. 25
1. 各臟器內的phGPX及GPX活性變化…………………………. 25
(1) 肝臟…………………………………………………………. 25
(2) 肺臟…………………………………………………………. 26
(3) 心臟…………………………………………………………. 26
(4) 腎臟…………………………………………………………. 27
(5) 睪丸…………………………………………………………. 28
(6) 腎上腺………………………………………………………. 28
(7) 紅血球………………………………………………………. 29
(8) 血漿…………………………………………………………. 29
2. Se-P……….……………………………………………………… 31
四、 病理切片………………………………………………………….. 32
五、 各氧化指標的變化……………………………………………….. 32
1. 各臟器中的TBARS含量……………………………………….. 32
(1) 肝臟………………………………………………………….. 32
(2) 肺臟…………………………………………………………. 33
(3) 心臟…………………………………………………………. 34
(4) 腎臟…………………………………………………………. 35
(5) 睪丸…………………………………………………………. 36
2. 各臟器中的carbonyl groups變化………………………………. 38
(1) 肝臟………………………………………………………….. 39
(2) 肺臟………………………………………………………….. 39
(3) 心臟………………………………………………………….. 39
(4) 腎臟………………………………………………………….. 39
(5) 睪丸………………………………………………………….. 39
3. 各臟器中的thiols含量變化…………………………………….. 40
(1) 肝臟………………………………………………………….. 40
(2) 肺臟………………………………………………………….. 40
(3) 心臟………………………………………………………….. 40
(4) 腎臟………………………………………………………….. 41
(5) 睪丸………………………………………………………….. 41
4. 各臟器中的GS活性的變化…………………………………….. 41
(1) 肝臟………………………………………………………….. 41
(2) 肺臟………………………………………………………….. 41
(3) 心臟………………………………………………………….. 42
(4) 腎臟………………………………………………………….. 42
(5) 睪丸………………………………………………………….. 42
5. 各臟器中的G-6PD活性變化………………………….………… 43
(1) 肝臟………………………………………………………….. 43
(2) 肺臟………………………………………………………….. 43
(3) 心臟………………………………………………………….. 43
(4) 腎臟………………………………………………………….. 44
(5) 睪丸………………………………………………………….. 44
6. 血漿LDH活性變化……………………………………………… 45
六、 其他參考資料……………………………………………… 45
1. 硒含量變化………………………………………………………. 45
(1) 肝臟………………………………………………………….. 45
(2) 肺臟………………………………………………………….. 45
(3) 心臟………………………………………………………….. 46
(4) 腎臟…………………………………………………………. 46
(5) 睪丸…………………………………………………………. 46
(6) 腎上腺………………………………………………………. 46
(7) 紅血球………………………………………………………. 47
(8) 血漿…………………………………………………………. 47
2. 各臟器中的維生素E變化………………………………………. 48
(1) 肝臟…………………………………………………………. 48
(2) 肺臟…………………………………………………………. 48
(3) 心臟…………………………………………………………. 49
(4) 睪丸…………………………………………………………. 49
第五章 討論………………………………………………………….……….. 104
一、資料對照…………………………………………………………… 104
1. 回顧…………………………………………………………….….. 104
2. 研究實際條件…………………………………………………… 105
二、整合討論……………………………………………………………. 106
1. 肝臟……………………………………………………………... 106
2. 肺臟……………………………………………………………... 107
3. 心臟……………………………………………………………... 108
4. 腎臟……………………………………………………………... 110
5. 睪丸……………………………………………………………... 111
6. 腎上腺…………………………………………………………... 112
7. 紅血球…………………………………………………………... 113
8. 血漿……………………………………………………………... 113
9. 展望……………………………………………………………... 115
第六章 結論…………………………………………………….………. 116
參考文獻………………………………………………………………… 118

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