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慢性阻塞性肺疾病患者肺组织中ATF3与ATF4对γ-GCS表达的影响

发布时间:2019-04-28 08:53
【摘要】:目的 探讨慢性阻塞性肺疾病(简称慢阻肺)患者肺组织中活化转录因子3(ATF3)、活化转录因子4(ATF4)的表达变化,以及ATF3和ATF4对γ-谷氨酰半胱氨酸合成酶(γ-GCS)表达的影响,探讨其在慢阻肺发病中的作用。方法 收集伴或不伴慢阻肺并行肺叶切除的肺癌患者临床肺组织标本40例(慢阻肺组和对照组各20例),取材标本均为远离原发肺癌病灶5 cm以上、肉眼观察无肺癌浸润的外周肺组织。所有患者术前均详细询问病史,进行体格检查、胸部X线片或肺部CT以及肺功能检测。应用原位杂交及免疫组化检测患者肺组织中ATF3、ATF4、γ-GCS重链亚基(γ-GCS-HS)m RNA及蛋白的表达,应用免疫共沉淀法(CO-IP)检测ATF3、ATF4与γ-GCS-HS蛋白之间的相互作用,并对ATF3、ATF4 m RNA及蛋白与γ-GCS-HS m RNA及蛋白进行相关分析。结果 慢阻肺患者肺组织中ATF3、ATF4、γ-GCS-HS m RNA及蛋白呈强阳性表达,较对照组显著升高(P0.01)。在γ-GCS-HS抗体捕获的免疫沉淀中,ATF3、ATF4抗体均可杂交出明显的蛋白条带,且慢阻肺组较对照组明显增强(P0.01)。相关分析显示肺组织中ATF3、ATF4蛋白表达与γ-GCS-HS m RNA及蛋白表达均呈明显正相关(P0.01);ATF3、ATF4、γ-GCS-HS蛋白表达与FEV1%pred、FEV1/FVC均呈明显正相关(P0.01)。结论 在慢阻肺患者发病过程中,氧化应激诱导转录因子ATF3和ATF4过表达,ATF3和ATF4可能通过影响γ-GCS m RNA和蛋白的表达而发挥抗氧化保护作用。
[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 纬-glutamylcysteine synthetase (纬-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, 纬-GCS heavy chain subunit (纬-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 纬-GCS-HS protein was studied, and the correlation between ATF3,ATF4 m RNA and 纬-GCS-HS m RNA and protein was analyzed. Results the positive expression of ATF3,ATF4, 纬-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 纬-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 纬-GCS-HS m RNA and protein in lung tissue (P0.01), and the expression of ATF3,ATF4, 纬-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 纬-GCS m RNA and protein.
【作者单位】: 湖南省人民医院湖南师范大学第一附属医院呼吸内科;湖南省老年医院呼吸疾病研究所;

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