慢性阻塞性肺疾病患者肺组织中PRMT6的表达及意义
发布时间:2019-06-08 13:22
【摘要】:目的:观察慢性阻塞性肺疾病(COPD)患者肺组织中蛋白精氨酸甲基转移酶6(Protein Arginine Methytransferase6, PRMT-6)、白介素(IL)-13、环氧合酶(COX)-2的mRNA表达情况,PRMT-6蛋白表达及组蛋白H3R2位点非对称双甲基化(H3R2me2a)和H3K4位点三甲基化(H3K4me3)信号水平情况,探讨PRMT6是否通过调控组蛋白甲基化而参与COPD炎症机制。 方法:本研究选取2012年8月至2013年1月在中南大学湘雅二医院及株洲中心医院(原株洲市一医院)胸外科因肺癌入院行肺段或肺叶切除术的患者31例(其中合并COPD者11例),标本均选取远离原发肿瘤病灶5cm以外且肉眼无癌细胞浸润的新鲜正常肺组织标本用于实验,所有入选组均未经放疗、化疗等处理,均无COPD以外的肺部疾病以及全身其他系统慢性病变。根据术前肺功能、吸烟习惯及COPD诊断标准将其分成三组:非吸烟非COPD组10例、吸烟非COPD组10例,吸烟COPD组(稳定期)11例。采用QRT-PCR检测PRMT6mRNA、IL-13mRNA、COX Ⅱ mRNA表达,同时Western-Blotting检测PRMT6蛋白表达及组蛋白H3R2me2a和H3K4me3信号水平。 结果:1、吸烟COPD组一秒钟用力呼气量占预计值%(FEV1%pre)、一秒率(FEV1/FVC%)及呼气峰值流速占预计值%(PEF%pre)较非吸烟非COPD组和吸烟非COPD组明显降低(p均0.01),而正常组与健康吸烟组间无显著性差异(p0.05)。 2、与非吸烟非COPD组相比,吸烟非COPD组及吸烟COPD组PRMT6mRNA表达显著降低(P0.01),而IL-13、COX-2的mRNA表达均增高(P0.01)。 3、与非吸烟非COPD组相比,吸烟非COPD组及吸烟COPD组PRMT6蛋白表达下降(P0.01),组蛋白H3R2me2a信号水平下降(P<0.01), H3K4me3信号水平升高(P0.01)。 结论:COPD患者肺组织中蛋白精氨酸甲基转移酶PRMT6表达下降,可能通过下调组蛋白H3R2me2a信号水平,而减少对组蛋白H3K4me3的拮抗,进而激活炎症基因IL-13、COX-2的转录表达,参与COPD的形成。
[Abstract]:Objective: to observe the mRNA expression of protein arginine methyltransferase 6 (Protein Arginine Methytransferase6, PRMT-6), IL (IL) 13 and cyclooxygenase (COX) 2 in lung tissue of patients with chronic obstructive pulmonary disease (COPD). The expression of PRMT-6 protein and the signal levels of asymmetric dimethylated (H3R2me2a) and trimethylated (H3K4me3) at histone H3R2 site were investigated to explore whether PRMT6 was involved in the inflammatory mechanism of COPD by regulating histone methylation. Methods: from August 2012 to January 2013, 31 patients (11 with COPD) underwent segmental or lobectomy for lung cancer in Xiangya No. 2 Hospital of Central South University and Zhuzhou Central Hospital (No. 1 Hospital of Zhuzhou City). Fresh normal lung tissue specimens far from the primary tumor focus 5cm and no cancer cell infiltration were selected for the experiment. All the selected groups were treated without radiotherapy and chemotherapy. There were no lung diseases other than COPD and chronic lesions of other systemic diseases. According to the preoperative pulmonary function, smoking habits and COPD diagnostic criteria, they were divided into three groups: non-smoking non-COPD group (n = 10), smoking non-COPD group (n = 10) and smoking COPD group (n = 11). The expression of PRMT6mRNA,IL-13mRNA,COX 鈪,
本文编号:2495315
[Abstract]:Objective: to observe the mRNA expression of protein arginine methyltransferase 6 (Protein Arginine Methytransferase6, PRMT-6), IL (IL) 13 and cyclooxygenase (COX) 2 in lung tissue of patients with chronic obstructive pulmonary disease (COPD). The expression of PRMT-6 protein and the signal levels of asymmetric dimethylated (H3R2me2a) and trimethylated (H3K4me3) at histone H3R2 site were investigated to explore whether PRMT6 was involved in the inflammatory mechanism of COPD by regulating histone methylation. Methods: from August 2012 to January 2013, 31 patients (11 with COPD) underwent segmental or lobectomy for lung cancer in Xiangya No. 2 Hospital of Central South University and Zhuzhou Central Hospital (No. 1 Hospital of Zhuzhou City). Fresh normal lung tissue specimens far from the primary tumor focus 5cm and no cancer cell infiltration were selected for the experiment. All the selected groups were treated without radiotherapy and chemotherapy. There were no lung diseases other than COPD and chronic lesions of other systemic diseases. According to the preoperative pulmonary function, smoking habits and COPD diagnostic criteria, they were divided into three groups: non-smoking non-COPD group (n = 10), smoking non-COPD group (n = 10) and smoking COPD group (n = 11). The expression of PRMT6mRNA,IL-13mRNA,COX 鈪,
本文编号:2495315
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