【摘要】：目的：觀察慢性阻塞性肺疾病(COPD)患者肺組織中蛋白精氨酸甲基轉(zhuǎn)移酶6(Protein Arginine Methytransferase6, PRMT-6)、白介素(IL)-13、環(huán)氧合酶(COX)-2的mRNA表達(dá)情況,PRMT-6蛋白表達(dá)及組蛋白H3R2位點(diǎn)非對(duì)稱(chēng)雙甲基化(H3R2me2a)和H3K4位點(diǎn)三甲基化(H3K4me3)信號(hào)水平情況,探討PRMT6是否通過(guò)調(diào)控組蛋白甲基化而參與COPD炎癥機(jī)制。 方法：本研究選取2012年8月至2013年1月在中南大學(xué)湘雅二醫(yī)院及株洲中心醫(yī)院(原株洲市一醫(yī)院)胸外科因肺癌入院行肺段或肺葉切除術(shù)的患者31例(其中合并COPD者11例),標(biāo)本均選取遠(yuǎn)離原發(fā)腫瘤病灶5cm以外且肉眼無(wú)癌細(xì)胞浸潤(rùn)的新鮮正常肺組織標(biāo)本用于實(shí)驗(yàn),所有入選組均未經(jīng)放療、化療等處理,均無(wú)COPD以外的肺部疾病以及全身其他系統(tǒng)慢性病變。根據(jù)術(shù)前肺功能、吸煙習(xí)慣及COPD診斷標(biāo)準(zhǔn)將其分成三組：非吸煙非COPD組10例、吸煙非COPD組10例,吸煙COPD組(穩(wěn)定期)11例。采用QRT-PCR檢測(cè)PRMT6mRNA、IL-13mRNA、COX Ⅱ mRNA表達(dá),同時(shí)Western-Blotting檢測(cè)PRMT6蛋白表達(dá)及組蛋白H3R2me2a和H3K4me3信號(hào)水平。 結(jié)果：1、吸煙COPD組一秒鐘用力呼氣量占預(yù)計(jì)值%(FEV1%pre)、一秒率(FEV1/FVC%)及呼氣峰值流速占預(yù)計(jì)值%(PEF%pre)較非吸煙非COPD組和吸煙非COPD組明顯降低(p均0.01),而正常組與健康吸煙組間無(wú)顯著性差異(p0.05)。 2、與非吸煙非COPD組相比,吸煙非COPD組及吸煙COPD組PRMT6mRNA表達(dá)顯著降低(P0.01),而IL-13、COX-2的mRNA表達(dá)均增高(P0.01)。 3、與非吸煙非COPD組相比,吸煙非COPD組及吸煙COPD組PRMT6蛋白表達(dá)下降(P0.01),組蛋白H3R2me2a信號(hào)水平下降(P＜0.01), H3K4me3信號(hào)水平升高(P0.01)。 結(jié)論：COPD患者肺組織中蛋白精氨酸甲基轉(zhuǎn)移酶PRMT6表達(dá)下降,可能通過(guò)下調(diào)組蛋白H3R2me2a信號(hào)水平,而減少對(duì)組蛋白H3K4me3的拮抗,進(jìn)而激活炎癥基因IL-13、COX-2的轉(zhuǎn)錄表達(dá),參與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，

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