[摘 要] 目的：探讨丹皮酚（Pae）通过调控果蝇zeste基因增强子同源物2/神经外营养蛋白4抗体/细胞周期蛋白依赖性激酶抑制因子2A（EZH2/NXPH4/CDKN2A）轴对肺癌A549细胞增殖、迁移和侵袭能力的影响。方法：以梯度浓度（0、6.25、12.5、25、50、100、200 µg/mL）的Pae处理肺癌A549细胞，采用CCK-8法确定干预浓度；将A549细胞分为对照组（未经任何处理的A549细胞）、Pae组（12.5 µg/mL Pae）、Pae + siEZH2组（转染siEZH2 + 12.5 µg/mL Pae）、Pae+siNC组（转染siNC + 12.5 µg/mL Pae）、Pae + vector NC组（转染vectorNC + 12.5 µg/mL Pae）、Pae + vectorEZH2组（转染vector EZH2+12.5 µg/mL Pae），予以相应的处理后，采用克隆形成实验检测细胞克隆数，流式细胞术检测细胞周期分布，Transwell实验检测细胞侵袭能力的变化，划痕实验检测细胞迁移能力的变化，流式细胞仪检测细胞凋亡情况，WB法检测EZH2、NXPH4、CDKN2A、Bcl-2和caspase-3蛋白表达量。在A549细胞中单独转染siEZH2或siNC，采用流式细胞仪测量细胞凋亡，WB法检测Bcl-2和caspase-3蛋白表达。建立A549细胞裸鼠移植瘤模型，评估Pae的体内抗肿瘤作用及其对相关蛋白表达的影响。结果：选择12.5 µg/mL为后续实验干预浓度。与对照组相比，Pae组细胞克隆数、S期细胞比例、迁移、侵袭能力以及EZH2、NXPH4和Bcl-2蛋白表达量显著降低，G0/G1期细胞比例、细胞凋亡率以及CDKN2A和caspase-3蛋白表达量明显升高（均P < 0.05）；与Pae + siNC组相比，Pae + siEZH2组细胞克隆数、S期细胞比例、迁移侵袭能力以及EZH2、NXPH4和Bcl-2蛋白表达量下降幅度更大，G0/G1期细胞比例、细胞凋亡率以及CDKN2A和caspase-3蛋白表达量升高幅度更大（P < 0.05）；与Pae+vectorNC组相比，Pae + vectorEZH2组细胞克隆数、S期细胞比例、迁移侵袭能力以及EZH2、NXPH4和Bcl-2蛋白表达量显著升高，G0/G1期细胞比例、细胞凋亡率以及CDKN2A和caspase-3蛋白表达量明显下降（P < 0.05）。敲低EZH2后A549细胞凋亡率和caspase-3表达明显上升，Bcl-2表达明显下降（P < 0.05）。体内实验表明Pae可显著降低肿瘤体积和质量且抑制EZH2/NXPH4/CDKN2A通路的活性。结论：Pae通过抑制EZH2/NXPH4/CDKN2A通路抑制A549细胞增殖、迁移和侵袭，诱导细胞凋亡。

【Objective】To evaluate the impact of prior use of inhaled corticosteroids（IC）on the clinical outcomes of chronic obstructive pulmonary disease patients hospitalised with community- acquired pneumonia （COPD- CAP）. 【Methods】This was a multicenter，retrospective study. Data of COPD-CAP patients from five teaching hospitals in Beijing，Shandong and Yunnan Provinces during 1st January 2013 through 31th December 2016 were reviewed. The patients with and without prior use of IC were compared，including demographic characteristics，clinical and radiologic features， and outcomes. A logistic regression model was conducted to explore the impact of prior IC use on the clinical outcomes of COPD-CAP patients. 【Results】Of 725 patients included in the study，13.9%（101/725）were prior IC users. Compared with no-IC users，IC users showed higher frequency of cardiovascular comorbidity（19.8% vs 12.7%）and a CAP history in the last year（20.8% vs 11.2%）；lower occurrence of pleural effusion（13.9% vs 23.7%）；more often classified in Global Initiative for Chronic Obstructive Lung Disease（GOLD）stage 3（35.1% vs 22.9%）and GOLD 4 stage（51.9% vs 21.8%），less often in GOLD 2 stage（10.4% vs 51.0%）. Adjusted by age，gender，underlying diseases，PSI/CURB-65 score and GOLD stage，logistic regression analysis confirmed prior IC use was associated with decreased risk for noninvasive ventilation［OR = 0.220，95% CI（0.052，0.926），P = 0.029］，but not with invasive ventilation［OR = 0.290，95% CI（0.068，1.236），P = 0.094］，needing vasopressor use［OR = 1.261，95% CI（0.456，3.485），P = 0.655］，ICU admission［OR = 1.455，95% CI（0.638，3.320），P = 0.373］and 30-day mortality［OR = 1.650，95% CI（0.575，2.838）， P = 0.352］.【Conclusion】Previous IC use has no major impact on the clinical outcomes of COPD-CAP patients.