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研究生:陳碧秋
研究生(外文):Bi-Chiou Chen
論文名稱:吸煙者及煙霧中大白鼠致肺病變之研究
論文名稱(外文):Study of actions and mechanisms of cigarette smoke
指導教授:蕭松瑞
指導教授(外文):Song-Jui Shiow
學位類別:碩士
校院名稱:中山醫學院
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:106
中文關鍵詞:吸煙者訊息傳遞
外文關鍵詞:8-nitroguaninesignaling proteins
相關次數:
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在過去的實驗中已發現氣體性NOx在人類肺纖維細胞中(MRC-5)中能夠誘導產生攻擊DNA的特異性產物---8-NO2-G。然而,香菸也會產出高濃度的ROS及NOx,但是否同樣會在吸煙者及煙霧中大白鼠產生,仍未被證實。為了證實在吸煙者血液中的DNA是否受到NOx的damage,我們選用15位輕度吸煙者(L-S), 每天1包,少於5年;21位中度吸煙者(M-S),每天2包,吸煙 5-10年;12位重度抽煙者(H-S),每天大於2包,吸煙超過10年;14位重度抽煙的肺癌患者(Cancer H-S)及12位不抽煙的健康者作為正常對照組,比較這些不同程度吸煙者其血中8-OH-dG和8-NO2-G形成的情形。果然,血中白血球數目、8-OH-dG 、8-NO2-G、血清中nitrite濃度及脂質過氧化產物MDA平均值,都隨著吸煙程度增加而增加,且有明顯劑量效應;而血清中抗氧化酵素SOD的活性亦隨之增加、然而GSH peroxidase的活性則是降低。
在動物實驗裡,將大白鼠分別曝露5、10、15支香煙煙霧中,每天2次、每次30分鐘、持續1個月,斷頸取其肺組織及血液分析DNA中8-NO2-G的量,與對照組比較,結果有明顯劑量效應,其量分別為0.17、1.65、23.50和37.58 ng/μg;且在血中白血球數目和血清中nitrite的濃度也都隨之增加。因此,香菸中的NOx或曝露而增加的內生性NO,所造成的DNA損傷(8-NO2-G的形成),可能與致癌作用有關。
此種oxidant stress damage 進一步以病理切片觀察暴露煙霧的大白鼠肺組織中terminal bronchiole及alveolar duct隨著暴露香煙數的增加,顯示出不同程度的lymphocytes infiltration在peribronchial region,都伴隨發炎現象或肺氣腫的產生。從以上證據顯示cigarette smoke引起肺組織之過氧化作用,造成肺組織之傷害,其作用可由8-OH-dG及8-NO2-G的形成來確認。
我們運用西方墨點法測定相關的訊息蛋白,進一步證實煙霧中的NOx在肺組織活化NF-κB及iNOS產生NO後,經由活化MEKK-1、JNK / P38訊息路徑,造成轉錄因子ATF-2蛋白表現增加,這個證據顯示,可能與煙霧中NOx造成肺組織癌化有關;除此對於Raf / MEK1路徑,則不相關。
關鍵詞:香煙、8-OH-dG、8-NO2-G、氮氧化物、訊息傳遞
Our previous studies have shown that 8-nitroguanine (8-NO2-G) could serve as a specific marker of DNA damage induced by gaseous nitrogen oxides (NOx). Furthermore, we investigated the potential of cigarette smoking containing NOx to generate 8-NO2-G in smoker and smoke exposed rats. To evaluate the effect of cigarette smoking on the NOx-caused DNA damage in blood samples of smokers, we compared the levels of 8-NO2-G in blood samples obtained from 15 light-smokers (L-S, less than 1pack/day), 21 moderate-smokers (M-S, 1-2 pack/day for 5-10 years), 12 heavy-smokers (H-S, over 2 packs/day for 10 years), 14 heavy smokers with lung cancer (cancer H-S) and 12 non-smoking healthy controls. The mean level of 8-NO2-G in blood from groups of L-S, M-S, H-S and cancer H-S, was higher than that of the 8-NO2-G levels and serum nitrite in smokers. Furthermore, in animal experiment, a dose-dependent increase in 8-NO2-G was observed in the DNA of rat lung and blood DNA after exposure to cigarette smoke twice a day, for 1 month. The level of 8-NO2-G is 0.17, 1.65, 23.50 and 37.58 ng per μg lung DNA for rat exposed with cigarette smoke from 0, 5, 10, 15 cigarettes, respectively. It was also found that white blood cell (WBC) count and serum concentration of nitrite increased after the smoke exposure. It is postulated that cigarette smoke-induced DNA damage (8-NO2-G formation) by exo- and endogenous NOx may constitute an important pathway in lung carcinogenesis.
Histopathological examination of the effect of gas-phase on the lung tissue in cigarette exposed rats. The terminal bronchiole was predominantly infiltrated by lymphocytes in the peribronchiolar region and mild to moderate degree of emphysema is noted in the alveolar space.
However, this project is to explore the tumor promoting effect of NOx on lung tumorgenesis.
目錄 ……………………………………………………………….. 1-2
縮寫表 …………………………………………………………….. 3
中文摘要…………………………………………………………… 4-5
英文摘要…………………………………………………………… 6-7
緒論及文獻整理…………………………………………………. 9-22
研究動機…………………………………………………………… 23
實驗設計…………………………………………………………… 24-25
實驗部份
(一) 血液及肺組織中8-nitroguanine之形成 ….. 26
壹、 材料及方法
一、實驗對象……………………………………………… 27
二、實驗材料
一) 化學試藥……………………………………….… 27
二) 儀器設備…………………………………………. 28-29
三、實驗方法……………………………………………… 30-37
四、實驗動物……………………………………………… 38
貳、結果………………………………………………………… 39-42
參、討論………………………………………………………… 43-45
肆、總結(Summary) …………………………………………… 46
伍、結果圖表(一)………………………………………… 47-56
(二)肺組織訊息傳遞及細胞週期蛋白之影響……. 57
文獻整理…………………………………………………………… 58-64
壹、材料及方法
一、動物處理……………………………………….……… 65
二、實驗材料
一) 化學試藥………………………………………….. 65
二) 儀器設備…………………………………………. 65-66
三、實驗方法………………………………………….….. 67-74
貳、結果……………………………………………………….. 75-78
參、討論……………………………………………………….. 78-81
肆、結果圖表(二)……………………………………….. 82-92
伍、總結 (Summary) ………………………………………... 93
參考文獻…………………………………………………. 94-106
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1. 蔡麗芳(民86)。女性母親角色的省思及諮商上的涵義。輔導季刊,第33卷,第1期,14-20。
2. 黃慧涵(民86)。女性、親密關係與憂鬱。輔導季刊,第33卷,第1期,21- 25。
3. 郭麗安(民83)。兩性對親密需求的差異及輔導對策。諮商與輔導,第107期,13-15。
4. 張英熙(民86)。男性特質與男性求助。輔導季刊,第33卷第4期,12-18。
5. 陳秉華 (民84)︰諮商中大學生的心理分離一個體化衝突改變歷程研究。國立台灣師範大學教育心理與輔導學系教育心理學報。28期,145-176頁。
6. 周麗玉(民86)國中個案輔導模式初探。諮商與輔導。137期。
7. 周麗玉(民82)需求的滿足與個我的改變--個我改變理論的探索。輔導季刊。第29卷。第五期。
8. 余德慧、蔡怡佳(民84):「離合」在青少年發展歷程的意義。在於楊國樞主編,親子關係與教化。台灣大學心理學系本土心理學研究室出版,桂冠圖書公司印製發行。台北。
9. 孫世維(民86)。親子依附與分離─個體化:大學時期的發展。教育與心理研究,第20期,271-296。
10. 王鍾和(民87)。談親子衝突及其因應之道。學生輔導,第57期,32-40。
11. 王鍾和(民86)。引導父親扮好親職角色。學生輔導,第52期,88-91。
12. 王行 (民85)。新男性的成長─打破「男性優勢」的迷失。測驗與輔導,135期,2784-2785。