慢性阻塞性肺疾病患者肺组织中蛋白精氨酸甲基转移酶6的表达及意义  

The Expression and Significance of Protein Arginine Methytransferase-6 in Lung Tissues of Patients with Chronic Obstructive Pulmonary Disease

作　　者：梁彦超[1] 陈哲[1] 王倩[1] 陈燕[1] 

机构地区：[1]中南大学湘雅二医院呼吸内科,湖南长沙410011

出　　处：《中国呼吸与危重监护杂志》2014年第4期334-337,共4页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家自然科学基金(编号:81270100)

摘　　要：目的观察慢性阻塞性肺疾病(简称慢阻肺)患者肺组织中蛋白精氨酸甲基转移酶6(PRMT6)的mRNA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慢阻肺的发病。方法选取胸外科因肺癌行肺叶切除术的患者31例,据术前肺功能、吸烟史及慢阻肺诊断标准将患者分成对照组(非吸烟非慢阻肺,n=10)、吸烟组(吸烟非慢阻肺,n=10)和吸烟慢阻肺组(n=11)。选取远离原发病灶5 cm以上、肉眼观察无肺癌浸润的外周肺组织,采用QRT-PCR检测PRMT6、白细胞介素13(IL-13)、环氧酶2(COX-2)的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。结果吸烟慢阻肺组FEV1%pred、FEV1/FVC及PEF%pred较对照组和吸烟组明显降低(P<0.05)。与对照组比较,吸烟组及吸烟慢阻肺组PRMT6 mRNA表达、PRMT6蛋白表达及组蛋白H3R2me2a信号水平均显著降低(P<0.01),而IL-13、COX-2的mRNA表达及H3K4me3信号水平均显著增高(P<0.01)。结论慢阻肺患者肺组织中PRMT6表达下降,可能通过下调组蛋白H3R2me2a信号水平而上调组蛋白H3K4me3的信号水平参与慢阻肺的形成。Objective To observe the expression levels of protein arginine methytransferase-6 （PRMT6） mRNA and the changes in histone H3K4me3 and H3R2me2a signal in lung tissues of patients with chronic obstructive pulmonary disease （ COPD ）, and explore the significance of PRMT6 in COPD. Methods According to the latest COPD diagnostic criteria, 31 COPD patients who had underwent pneumonectomy were divided into 3 groups, ie. 10 non-smokers without COPD, 10 smokers without COPD, and 11 smokers with COPD （in stable stage）. The peripheral lung tissues 5cm far away from the primary tumor on gross examination were sampled. QRT-PCR was used to measure PRMT6 mRNA and inflammatory genes expression. Western-blot was used to measure PRMT6, histone H3K4me3 and H3R2me2a protein. Results The FEV1%pred,FEVI/FVC and PEF%pred in the smokers with COPD were significantly lower than those in the smokers without COPD and non-smokers without COPD. Compared with the non-smokers without COPD,the mRNA and protein expression of PRMT6 and histone H3R2me2a expression decreased significantly （P 〈0. 05）,but IL-13 and COX-2 gene mRNA expressions and histone H3K4me3 expression increased significantly （P 〈 0. 05 ） in the smokers with or without COPD. Conclusions The expression of PRMT6 decreases in lung tissue of COPD patients. PRMT6 may be involved in the COPD pathogenesis through down-regnlation of histone H3R2me2a signal so that to reduce the antagonism on histone H3K4me3.

关 键 词：慢性阻塞性肺疾病 蛋白精氨酸甲基转移酶6 组蛋白H3R2位点非对称双甲 基化 H3K4位点三甲基化 

分 类 号：R563.9[医药卫生—呼吸系统]