PRMT6过表达在NF-κB/p65介导小鼠肺气肿炎症反应中的作用

Role of PRMT6 overexpression in NF-κB/p65 mediated inflammatory response in mice with emphysema

[目的]观察蛋白精氨酸甲基转移酶6(PRMT6)过表达在NF-κB/p65介导小鼠肺气肿模型炎症反应中的作用及机制。[方法]80只Balb/c小鼠暴露于香烟烟雾建立肺气肿模型,随机分为阴性对照组、模型组、阳性对照组(空白慢病毒载体气管内滴注)和PRMT6过表达组(PRMT6慢病毒载体气管内滴注)各20只。HE法观察肺组织形态学,Western Blot测定肺组织PRMT6表达。ELISA测定肺泡灌洗液(BALF)和肺组织匀浆中肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)水平。[结果]与阴性对照组比较,模型组和阳性对照组小鼠气道阻力、BALF和肺组织匀浆TNF-α及IL-8水平、肺组织NF-κB/p65表达均升高,动态肺顺应性、肺组织PRMT6相对表达量降低(P<0.05);与模型组和阳性对照组比较,PRMT6过表达组小鼠气道阻力、BALF和肺组织匀浆TNF-α及IL-8水平、肺组织NF-κB/p65表达降低,动态肺顺应性、肺组织PRMT6相对表达水平升高(P<0.05)。[结论]PRMT6过表达可能通过抑制肺气肿小鼠肺组织NF-κB/p65核转位,发挥抗炎作用,改善肺功能。

[Objective]To investigate role and mechanism of protein arginine methyltransferase 6(PRMT6) overexpression in NF-κB/p65 mediated inflammatory responsein mice with emphysema. [Method]Eighty Balb/c mice were exposed to mainstreamcigarette smoke to induce emphysema models, and randomly divided into negative control group, model group, positive control group and PRMT6 overexpression group, each with 20 mice. Mice in positive control group and PRMT6 overexpression group were instilled intratracheallywith blank lentiviral vector and PRMT6 lentiviral vector respectively.The morphological changes of lung tissue were observed by HE method, and PRMT6 expression in lung tissue was determined by Western Blotting. Enzyme-linked immunosorbent assay was used to determine the levels of tumor necrosis factor-α(TNF-α) and interleukin-8(IL-8) in bronchoalveolar lavage fluid(BALF) and lung tissue homogenate. [Result]Compared with the negative control group, the airway resistance, TNF-α and IL-8 levels in BALF and lung homogenates, NF-κB/p65 expression in lung tissues were increased, and the dynamic lung compliance and relative expression of PRMT6 in lung tissues were decreased in the model group and the positive control group(P<0.05).Compared with the model group andthe positive control group, the airway resistance, TNF-α and IL-8 levels in BALF and lung homogenates, NF-κB/p65 expression in lung tissues were decreased, and the dynamic lung compliance and relative expression levels of PRMT6 in lung tissues were increased in the PRMT6 overexpression group(P<0.05).[Conclusion]PRMT6 overexpression may play an anti-inflammatory role and improve lung function by inhibiting NF-κB/p65 nuclear transposition in emphysema mice.