臺灣博碩士論文加值系統

本研究探討六株雙叉桿菌 Bifidobacterium adolescentis BCRC14606、B. bifidum BCRC14615、B. breve BCRC11846、B. infantis BCRC14602、B. lactis Bb-12 與 B. longum BCRC14634 對活性氧物質的抗致突變性。使用安氏試驗法之測試菌株 Salmonella typhimurium TA102 來分析雙叉桿菌胞內物對氧化突變劑 tert-butylhydroperoxide (t-BOOH) 與過氧化氫 (H2O2) 誘導突變之防禦效果。結果顯示六株雙叉桿菌菌體懸浮液 (1010 CFU/mL) 經超音波破碎，離心 (15,000 × g, 30 min) 移除細胞碎片後所得到的胞內物，對 t-BOOH 和 H2O2 之抗致突變性分別為 15.9-50.9 % 和 51.5-72.3 %。更進一步研究結果顯示抗致突變性的主要機制為去致突變作用。而雙叉桿菌的抗氧化變異性可能歸因於其抗氧化能力，所以進一步評估其抗氧化性，檢測系統包括還原力、螫合亞鐵離子能力、DPPH 自由基及活性氧物質之清除能力探討。結果顯示六株雙叉桿菌之胞內物都表現出良好的還原力，以 B. lactis 表現最好，其還原力相當於 328 μg/mL 的抗壞血酸。清除 DPPH 自由基測定中，則以 B. longum 清除能力最好。螫合亞鐵離子方面，6 株雙叉桿菌胞內物表現出 34-52 % 之螫合力，以B. longum最佳。在清除活性氧物質方面，胞內物均具有清除超氧陰離子之能力，清除率介於 52.7-69.9 %，而以 B. adolescentis 效果最好；對過氧化氫之清除率則在 5.0-18.0 % 之間，其中以 B. bifidum有較佳表現；而在清除羥基自由基方面，B. bifidum 具有 11.8 % 之清除力，為 6 株雙叉桿菌中表現最佳者。

Antimutagenic activities of intracellular extracts of Bifidobacterium adolescentis BCRC14606, B. bifidum BCRC14615, B. breve BCRC11846, B. infantis BCRC14602, B. lactis Bb-12 and B. longum BCRC14634 against reactive oxygen substances were studied by a modified Ames test using Salmonella typhimurium TA102 as a test strain. The intracellular extracts were prepared by disrupting cells (1010 CFU/mL) with an ultrasonic disrupter and subsequently removing cell debris by centrifugation at 15,000 × g for 30 min. Assays for the ability of intracellular extracts of bifidobacteria against mutations induced by peroxide mutagens tert-butylhydroperoxide (t-BOOH, 10μg/plate) and hydrogen peroxide (H2O2, 6μmol/plate) toward S. typhimurium TA102 were developed. Results showed that the antimutagenic activities of bifidobacteria against t-BOOH and H2O2 were 15.9-50.9% and 51.5-72.3%, respectively. It was further shown that main mechanism of antimutagenicity is desmutagenic effect. The antimutagenic activities of bifidobacteria were probably attributed to their antioxidative activities. Therefore, antioxidative activities of these bifidobacteria were further determined by measuring their reducing activity, ferrous ion chelating activity, α-diphenyl-2-picryl hydrazyl (DPPH) radical and reactive oxygen species scavenging activity. All bifidobacteria showed excellent reducing activity; among them B. lactis Bb-12 gave the highest reducing activity. B. longum had the highest scavenging DPPH radical ability. The chelating effects of six bifidobacteria on ferrous ion ranged from 34 to 52%; B. longum had the best chelating effects. With respect to scavenge reactive oxygen species, the scavenging effects on superoxide anions ranged from 52.7 to 69.9%; B. adolescentis showed the best superoxide anion scavenging ability. The scavenging effects on hydrogen peroxide by six bifidobacteria were 5.0 to 18.0% and B. bifidum showed the highest scavenging ability. B. bifidum displayed 11.8% hydroxyl radical scavenging activity, which was the greatest ability among six strains tested.

壹、前言………………………………………………………………….1
貳、文獻整理…………………………………………………………….3
一、 雙叉桿菌簡介………………………………………………….3
二、 雙叉桿菌之生理機能………………………………………….4
（一） 維持腸道內正常微生物菌相……………………………5
（二） 促進乳酸之代謝……………………………………….7
（三） 改善乳糖不耐症………………………………………7
（四） 提高營養價值……….…………………………………7
（五） 合成維生素………………….………………………….8
（六） 降低血膽固醇…………………………………………..8
（七） 保肝作用………………..……………………….……..9
（八） 活化免疫系統……………………………………………9
（九） 抗腫瘤活性…………………………………………….10
三、 雙叉桿菌之抗氧化性……………………………..………….11
四、 雙叉桿菌之抗致突變性……………………………………..12
五、 活性氧與自由基之特性…………………………..…..……14
（一） 超氧陰離子..…………………………………..………..18
（二） 羥基自由基……………………………………………18
（三） 過氧化氫………………………………………………19
（四） 單重態氧……….…………………………….…………19
（五） 過氧化自由基及烷氧自由基……………….………….20
六、 自由基對生物體之傷害……………………………………20
（一） 對脂質的影響…………………………………..…..20
（二） 對核酸的影響…………………………………………21
（三） 對蛋白質的影響………………………………………22
（四） 對醣類的影響..…………………………….…………22
七、 氧化壓力……………...………………………………………23
（一） 氧化壓力與疾病………………………………………..23
（二） 氧化壓力與致癌作用…………………………...……24
八、 抗氧化防禦系統……………………………….………….….26
（一） 抗氧化酵素……………………………………………..26
（二） 抗氧化劑………………………………………………28
（三） 修復系統……………………………………………...31
九、 抗氧化劑之抗致癌作用…………………………………….32
十、 膳食與癌症…………………………………………………...33
（一） 食物中之致突變物/致癌物…………………………..34
（二） 食品中之抗致突變物/抗致癌物………………………38
（三） 抗致突變物/抗致癌物之作用機制…………………….39
十一、 安氏試驗法……………………………………………...44
（一） S. typhimurium TA102 之介紹………………………..47
（二） t-butyl hydroperoxide之介紹…………………………47
十二、 實驗架構…………………………….………...……….….51
參、材料與方法……………………………………………………...…52
一、 實驗材料……………………………………………………52
（一） 試驗菌株………………………………………………52
（二） 培養基…………………………………………………52
（三） 儀器……………………………………………………..52
（四） 藥品……………………………………………………53
二、 實驗方法…………………………………………………..…54
（一） 菌種的活化及保存……………………………….…….54
（二） 雙叉桿菌的菌數計數…………………………………..54
（三） 雙叉桿菌胞內物之製備…………………………….….55
（四） S. typhimurium TA 102試驗菌株基因形態之確認…....55
1. 組胺酸要求性之確認…………………………………55
2. rfa 突變之測試.……………………………………….57
3. uvrB 突變之測試…………………………………….57
4. R-factor 之測試……………………………………….58
5. pAQ1 plasmid 之測試……………………………….58
（五） 雙叉桿菌之抗致突變性………………………………59
1. 毒性試驗………………………………………………59
2. 致突變性試驗………………………………………….59
3. 抗致突變性試驗……………………………………….60
4. 分段式組合評估雙叉桿菌抗致突變之機制………….61
（六） 雙叉桿菌之抗氧化性…………………………………..63
1. 還原力之測定………………………………………….63
2. 螫合亞鐵離子能力之測定…………………….……..63
3. 清除 DPPH 自由基能力之測定…………………...…64
4. 超氧陰離子清除效應………………………………….64
5. 過氧化氫清除效應……………………………………64
6. 羥基自由基的清除效應……………………………….65
三、統計分析……………………………………………………….65
肆、結果與討論…………………………………………………………66
一、 S. typhimurium TA 102試驗菌株
基因形態之確認………………………………………….….66
(一) 組胺酸需求性之確認…………………………………66
(二) rfa 突變之測試………………………..………………66
(三) uvrB 突變之測試………………………….…………..68
(四) R-factor 之測試………………………………….……68
(五) pAQ1 plasmid 之測試………………………………...68
二、 雙叉桿菌對 S. typhimurium TA 102 之毒性試驗及
致突變性試驗……………………………….……………….69
(一) 毒性試驗………………………………………………69
(二) 致突變試驗……………………………………………69
三、 雙叉桿菌之抗致突變性………………………….…………71
(一) 雙叉桿菌胞內物對 t-butyl hydroperoxide誘導
S. typhimurium TA 102 氧化變異之抑制效果…….…71
(二) 雙叉桿菌胞內物對 H2O2 誘導 S. typhimurium
TA 102 氧化變異之抑制效果………………………...73
四、 雙叉桿菌抗致突變機制之探討……………………………75
(一) 雙叉桿菌胞內物與 t-BOOH 經不同預反應處理後
對誘導 S. typhimurium TA 102 氧化變異之影響…...75
(二) 雙叉桿菌胞內物與 H2O2 經不同預反應處理後對
誘導 S. typhimurium TA 102 氧化變異之影響……...80
五、 雙叉桿菌之抗氧化性………………………………………87
(一) 還原力之測定…………………………………………87
(二) 螫合亞鐵離子能力之測定……………………………90
(三) 清除 DPPH 自由基能力之測定……………………..91
(四) 清除超氧陰離子能力測定……………………………93
(五) 清除過氧化氫之能力…………………………………95
(六) 清除羥基自由基之能力…………………………..…..97
伍、結論………………………………………………………………101
參考文獻……………………………………………………………103
表 次
頁次
表一、目前已使用之益生菌………..……………………………………6
表二、活性氧和相關化合物例子………………………………………16
表三、自由基之例子…………………..………………………….…….17
表四、常用的 Salmonella 測試菌株之基因型態……...……………...46
表五、S. typhimurium TA 102試驗菌株之基因型態………………….67
表六、雙叉桿菌胞內物對 S. typhimurium TA 102 之毒性及致突
變性………………..………………………………………..…..70
表七、雙叉桿菌胞內物對 t-BOOH 誘導 S. typhimurium TA 102
致突變性之抑制效果……………………………………….….72
表八、雙叉桿菌胞內物對 H2O2 誘導 S. typhimurium TA 102
致突變性之抑制效果……………………………………....…..74
表九、雙叉桿菌胞內物與 t-BOOH 預反應對致突變性之影響……76
表十、雙叉桿菌胞內物與 S. typhimurium TA102 預反應對
t-BOOH 致突變性之影響……………………….…………….78
表十一、S. typhimurium TA102 與 t-BOOH 預反應對致突變性
之影響………………………………………………..………79
表十二、雙叉桿菌胞內物與 H2O2 預反應對致突變性之影響……..81
表十三、雙叉桿菌胞內物與 S. typhimurium TA102 預反應對
H2O2 致突變性之影響…………………………...…………..82
表十四、S. typhimurium TA102 與 H2O2 預反應對致突變性之
影響…………………………………………………………..84
表十五、雙叉桿菌胞內物與 S. typhimurium TA102 經不同反應
步驟處理後對 H2O2 致突變之影響……………………….85
表十六、雙叉桿菌胞內物與 S. typhimurium TA102 經不同反應
步驟處理後對 t-BOOH 致突變之影響…………………..86
表十七、雙叉桿菌胞內物之還原力……………………………….…...89
表十八、雙叉桿菌胞內物對亞鐵離子之螫合能力…….……………...92
表十九、雙叉桿菌胞內物對 DPPH 自由基之清除能力……………..94
表二十、雙叉桿菌胞內物對超氧陰離子自由基之清除能力………....96
表二十一、雙叉桿菌胞內物對過氧化氫之清除能力…………………98
表二十二、雙叉桿菌胞內物對羥基自由基之清除能力……………..100
圖次
頁次
圖一、三重態氧分子形成活性氧之流程….…………….……………..15
圖二、西方膳食中常見之致癌物質的結構………….……………..….36
圖三、致突變過程中致突變物與抗致突變物之交互作用….………...41
圖四、抗致突變物之分類………………………………………………42
圖五、安氏之細菌分析法…….………………………………………...45
圖六、大鼠肝細胞中以 t-BOOH 誘導氧化壓力產生之機制……......49
圖七、以不同預培養步驟分析抗致突變之機制…………...………….62

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