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  本文選題：吸煙 + γ-谷氨酰半胱氨酸合成酶　； 參考：《山西醫(yī)科大學》2011年碩士論文

【摘要】：目的：(1)研究觀察不同吸煙時間對大鼠支氣管上皮細胞γ-谷氨酰半胱氨酸合成酶(γ-GCS)和轉錄因子激活蛋白-1(AP-1)表達的影響以及二者的相關性。(2)研究觀察吸煙對人氣道上皮細胞γ-谷氨酰半胱氨酸合成酶(γ-GCS)表達的影響,探討γ-GCS在吸煙所致慢性氣道炎癥及氧化／抗氧化失衡中的作用機制。 方法：(1)自制大鼠實驗性被動吸煙裝置,建立吸煙引起慢性氣道炎癥的動物模型,將40只大鼠隨機分為不吸煙組、吸煙1月組、吸煙2月組、吸煙3月組,每組各10只。分別采用免疫組織化學法檢測支氣管上皮細胞γ-GCS和AP-1(c-fos和c-jun)蛋白的表達水平。(2)選自2007年9月-2008年10月行支氣管鏡檢查的患者。吸煙指數300支,平均年齡50±10歲。共60例,分為4組：吸煙組(慢性支氣管炎組、非慢性支氣管炎組),不吸煙組(慢性支氣管炎組、非慢性支氣管炎組),每組各15例。通過支氣管鏡刷檢獲取支氣管氣道上皮細胞,采用免疫細胞化學法檢測支氣管上皮細胞中γ-GCS蛋白的表達水平。實驗數據應用SPSSl1.0軟件進行統計。 結果：1.香煙對大鼠支氣管上皮細胞γ-GCS表達的影響：(1)吸煙3月組大鼠出現了肺氣腫的病理改變；吸煙1月、2月和3月組大鼠支氣管上皮細胞γ-GCS蛋白表達的水平較不吸煙組明顯增高,差異有顯著性(P均0.01),(2)吸煙各組大鼠支氣管上皮細胞c-fos. c-Jun蛋白的表達水平均較不吸煙組明顯增高,差異有顯著性(P均0.01),吸煙各組間比較差異亦有顯著性(P分別0.01)；(3)吸煙1月組大鼠支氣管上皮細胞c-fos與c-jun蛋白的表達水平成直線正相關(r值分別為0.679、0.735；P值分別為0.031、0.015);c-fos與γ-GCS蛋白的表達水平成直線正相關(r值分別為0.703、0.724;P值分別為0.023、0.018);c-jun與γ-GCS蛋白的表達水平成直線正相關(r值分別為0.641、0.747；P值分別為0.046、0.013)；(4)吸煙3月組大鼠支氣管上皮細胞c-fos與c-jun蛋白的表達水平成直線正相關(r值分別為0.636、0.698;P值分別為0.048、0.025)；c-fos、c-jun與γ-GCS蛋白的表達水平無直線相關關系。2.吸煙對人氣道上皮細胞γ-GCS表達的影響：在氣管鏡下取人氣道上皮細胞,各組氣道上皮細胞γ-GCSh的表達：(1)吸煙組(慢性支氣管炎組(0.198±0.097)、非慢性支氣管炎組(0.346±0.113))的氣道上皮細胞γ-GCS的表達水平,低于不吸煙組(慢性支氣管炎組(0.403±0.102)、非慢性支氣管炎組(0.518±0.150))差異均有統計學意義(P均0.05)；(2)慢性支氣管炎組(0.403±0.102)的氣道上皮細胞Y-GCS的表達水平,低于非慢性支氣管炎組(0.498±0.150)的表達,差異有統計學意義(P0.05)。 結論：1.隨著吸煙時間的延長,大鼠支氣管上皮細胞中γ-GCS蛋白表達水平逐漸增高；c-fos和c-jun二者的表達也逐漸增高,并且呈正相關；2.但吸煙者人氣道內上皮細胞γ-GCS的免疫活性降低,γ-GCS在不吸煙非慢性支氣管炎者表達最強,而在吸煙者與慢性支氣管炎者的氣道內表達出現下調；γ-GCS在香煙所致慢性氣道炎癥、氧化應激及氧化/抗氧化失衡中可能發(fā)揮一定的作用；調控γ-GCS和維持GSH水平,對于抗氧化治療COPD還有待與進一步研究。
[Abstract]:Objective: (1) to investigate the effects of different smoking time on the expression of gamma glutamyl cysteine synthetase (gamma -GCS) and transcription factor activator -1 (AP-1) in the bronchial epithelial cells of rats and the correlation between the two. (2) the effects of smoking on the expression of gamma glutamyl cysteine synthetase (gamma -GCS) in human airway epithelial cells were investigated and studied. The role of GCS in chronic airway inflammation and oxidative / antioxidant imbalance induced by smoking.
Methods: (1) an experimental passive smoking device of self-made rats was established to establish an animal model of chronic airway inflammation caused by smoking. 40 rats were randomly divided into non smoking group, smoking January group, smoking February group, smoking March group, and 10 rats in each group. Immunohistochemistry was used to detect the protein of gamma -GCS and AP-1 (c-fos and c-jun) in bronchial epithelial cells respectively. (2) a total of 300 smoking indexes, with an average age of 50 + 10 years, were selected from September 2007 -2008 in October. A total of 60 cases were divided into 4 groups: smoking group (chronic bronchitis group, non chronic bronchitis group), non smoking group (chronic bronchitis group, non chronic bronchitis group), 15 cases in each group. Bronchoscopic brush examination The bronchial epithelial cells were obtained and the expression of gamma -GCS protein in bronchial epithelial cells was detected by immunocytochemistry. The experimental data were calculated by SPSSl1.0 software.
Results: 1. the effect of 1. cigarettes on the expression of gamma -GCS in the bronchial epithelial cells of rats: (1) the pathological changes of emphysema appeared in the rats in the March group of smoking, and the level of the expression of gamma -GCS protein in the bronchial epithelial cells of the rats in January, February and March was significantly higher than that in the non smoking group (P 0.01), and (2) on the bronchi of the rats in each group of smoking. The expression level of c-fos. c-Jun protein in the skin cells was significantly higher than that in the non smoking group (P 0.01), and the difference in smoking groups was also significant (P, respectively 0.01). (3) the expression level of c-fos and c-jun protein in the bronchial epithelial cells of the January group of smoking rats was positively correlated (r value was 0.679,0.735; P value was 0 respectively). 31,0.015); c-fos was positively correlated with the expression level of gamma -GCS protein (r value was 0.703,0.724; P value was 0.023,0.018 respectively); c-jun and the expression level of gamma -GCS protein were straight line correlation (r value was 0.641,0.747; P values were respectively); (4) the expression water of bronchial epithelial cells in smoking rats in March Positive correlation (r value 0.636,0.698, P value respectively 0.048,0.025); c-fos, c-jun and gamma -GCS protein expression level no linear correlation between.2. smoking on human airway epithelial cell gamma -GCS expression: airway epithelial cells under the trachea, the expression of gamma -GCSh in each group of airway epithelial cells: (1) smoking group (chronic Branch) The expression level of gamma -GCS in airway epithelial cells in the tracheitis group (0.198 + 0.097) and non chronic bronchitis group (0.346 + 0.113) was lower than that in the non smoking group (0.403 + 0.102) and non chronic bronchitis group (0.518 + 0.150). (2) the airway epithelium of chronic bronchitis group (2) was (0.403 + 0.102). The expression level of Y-GCS was lower than that in non chronic bronchitis group (0.498 + 0.150), and the difference was statistically significant (P0.05).
Conclusion: 1. with the prolongation of smoking time, the expression level of gamma -GCS protein in the bronchial epithelial cells of rats increased gradually, and the expression of c-fos and c-jun two increased gradually, and was positively correlated. 2. but the immune activity of gamma -GCS in the airway epithelial cells of smokers decreased, and the expression of gamma -GCS was the strongest in non smoking non chronic bronchitis. The expression of the airway in smokers and chronic bronchitis is downregulated, and gamma -GCS may play a role in chronic airway inflammation, oxidative stress and oxidation / antioxidant imbalance caused by cigarettes, and the regulation of gamma -GCS and the maintenance of GSH levels are still to be studied for antioxidant treatment of COPD.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R363

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