【摘要】：目的 探討慢性阻塞性肺疾病(簡稱慢阻肺)患者肺組織中活化轉錄因子3(ATF3)、活化轉錄因子4(ATF4)的表達變化,以及ATF3和ATF4對γ-谷氨酰半胱氨酸合成酶(γ-GCS)表達的影響,探討其在慢阻肺發(fā)病中的作用。方法 收集伴或不伴慢阻肺并行肺葉切除的肺癌患者臨床肺組織標本40例(慢阻肺組和對照組各20例),取材標本均為遠離原發(fā)肺癌病灶5 cm以上、肉眼觀察無肺癌浸潤的外周肺組織。所有患者術前均詳細詢問病史,進行體格檢查、胸部X線片或肺部CT以及肺功能檢測。應用原位雜交及免疫組化檢測患者肺組織中ATF3、ATF4、γ-GCS重鏈亞基(γ-GCS-HS)m RNA及蛋白的表達,應用免疫共沉淀法(CO-IP)檢測ATF3、ATF4與γ-GCS-HS蛋白之間的相互作用,并對ATF3、ATF4 m RNA及蛋白與γ-GCS-HS m RNA及蛋白進行相關分析。結果 慢阻肺患者肺組織中ATF3、ATF4、γ-GCS-HS m RNA及蛋白呈強陽性表達,較對照組顯著升高(P0.01)。在γ-GCS-HS抗體捕獲的免疫沉淀中,ATF3、ATF4抗體均可雜交出明顯的蛋白條帶,且慢阻肺組較對照組明顯增強(P0.01)。相關分析顯示肺組織中ATF3、ATF4蛋白表達與γ-GCS-HS m RNA及蛋白表達均呈明顯正相關(P0.01);ATF3、ATF4、γ-GCS-HS蛋白表達與FEV1%pred、FEV1/FVC均呈明顯正相關(P0.01)。結論 在慢阻肺患者發(fā)病過程中,氧化應激誘導轉錄因子ATF3和ATF4過表達,ATF3和ATF4可能通過影響γ-GCS m RNA和蛋白的表達而發(fā)揮抗氧化保護作用。
[Abstract]:Objective to investigate the expression of activated transcription factor 3 (ATF3) and activated transcription factor 4 (ATF4) in lung tissue of patients with chronic obstructive pulmonary disease (COPD). The effects of ATF3 and ATF4 on the expression of 緯-glutamylcysteine synthetase (緯-GCS) were studied. Methods 40 cases of lung cancer (20 cases of COPD group and 20 cases of control group) with or without chronic lung obstruction and lobectomy were collected. All the samples were more than 5 cm away from the primary lung cancer focus. The peripheral lung tissue without lung cancer infiltration was observed by naked eye. All patients were given detailed medical history, physical examination, chest X-ray or lung CT and pulmonary function test. In situ hybridization and immunohistochemistry were used to detect the expression of ATF3,ATF4, 緯-GCS heavy chain subunit (緯-GCS-HS) m RNA) and protein in lung tissue of patients, and ATF3, was detected by immunoprecipitation method (CO-IP). The interaction between ATF4 and 緯-GCS-HS protein was studied, and the correlation between ATF3,ATF4 m RNA and 緯-GCS-HS m RNA and protein was analyzed. Results the positive expression of ATF3,ATF4, 緯-GCS-HS m RNA and protein in lung tissue of patients with chronic obstructive pulmonary disease was significantly higher than that in control group (P0.01). In the immunoprecipitation captured by 緯-GCS-HS antibody, the protein bands could be hybridized by ATF3,ATF4 antibody, and the protein bands in the chronic obstructive lung group were significantly higher than those in the control group (P0.01). Correlation analysis showed that the expression of ATF3,ATF4 protein was positively correlated with the expression of 緯-GCS-HS m RNA and protein in lung tissue (P0.01), and the expression of ATF3,ATF4, 緯-GCS-HS protein was positively correlated with FEV1%pred,FEV1/FVC (P0.01). Conclusion oxidative stress induces over-expression of transcription factors ATF3 and ATF4 in the pathogenesis of chronic obstructive pulmonary disease. ATF3 and ATF4 may play an anti-oxidative protective role by affecting the expression of 緯-GCS m RNA and protein.
【作者單位】： 湖南省人民醫(yī)院湖南師范大學第一附屬醫(yī)院呼吸內科;湖南省老年醫(yī)院呼吸疾病研究所;

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