摘要目的 探讨组蛋白去乙酰化酶在特发性肺纤维化(IPF)和隐源性机化性肺炎(COP)发病机制中的作用.方法 收集2018年3-10月在北京协和医院呼吸科确诊的IPF患者15例(IPF组),男14例,女1例,年龄40～73岁,平均(59±8)岁;7例尚未治疗,6例正在使用吡非尼酮,2例使用N-乙酰半胱氨酸.COP患者15例(COP组),男5例,女10例,年龄41～71岁,平均(59±8)岁;7例尚未治疗,7例使用糖皮质激素,1例使用克拉霉素.同期无呼吸道疾病的体检者15例(对照组),男4例,女11例,年龄43～70岁,平均(58±6)岁.采集外周血并分离外周血单个核细胞(PBMC)进行核质分离,通过荧光法测定组蛋白去乙酰化酶总体活性,并分析其与各组主要实验室指标及肺功能参数的相关性.结果 IPF组和COP组PBMC胞质蛋白中组蛋白去乙酰化酶活性分别为(724±216)、(718±245) nmol/L,高于对照组的(409±105) nmol/L(均P＜0.01).IPF组和COP组核蛋白组蛋白去乙酰化酶活性分别为(2 309±708)和(3 310±1 005) nmol/L,高于对照的(1 572±611) nmol/L(均P＜0.01).COP患者PBMC核蛋白中组蛋白去乙酰化酶活性高于IPF患者(Z=-2.840,P=0.005).PBMC核蛋白中组蛋白去乙酰化酶活性与IPF患者FEV1占预计值％和D.CO占预计值％呈负相关(r=-0.574,P=0.025;r=-0.583,P=0.029),与COP患者FVC占预计值％和肺总量占预计值％(TLC占预计值％)呈负相关(r=-0.846,P=0.016;r=-0.900,P=0.015).结论 组蛋白去乙酰化酶可能参与了COP及IPF的发病过程.

abstractsObjective To explore the role of histone deacetylases(HDAC) in the pathogenesis of idiopathic pulmonary fibrosis(IPF) and cryptogenic organizing pneumonia(COP).Methods Fifteen IPF patients [14 males and lfemale,age 40-73 years,mean age (59±8) years] and 15 COP patients [5 males and 10 females,age 41-71 years,mean age (59±8) years] from Peking Union Medical College Hospital were recruited from March 2018 to October 2018.Fifteen healthy donors[4 males and 11fernales,age 43-70 years,mean age (58±6) years] were enrolled as controls.Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation.The nuclear and cytoplasmic proteins were extracted by Nuclear Extraction Kit.HDAC activity was measured by fluorimetric method.The relations between HDAC activity and clinical parameters were analyzed with SPSS.Results The HDAC activity of cytoplasmic protein and nuclear protein from patients with IPF were (724±216) nmol/L and (2 309±708) nmol/L,which were higher than that of health controls (409±105) nmol/L and (1 572±611) nmol/L (P＜0.01 for both).So as to the HDAC activity of cytoplasmic protein and nuclear protein from patients with COP which were (718±245) nmol/L and (3 310±1 005) nmol/L (P＜0.01 for both).The HDAC activity of nuclear protein from COP patients was higher than that from IPF patients (Z=-2.840,P=O.O05).The HDAC activity of nuclear protein was negatively correlated with FEV1 and DLCO in IPF patients (r=-0.574,P=0.025;r=-0.583,P=0.029),and negatively correlated with FVC and TLC in COP patients(r=-0.846,P=0.016;r=-0.900,P=0.015).Conclusion HDAC may be involved in the pathogenesis of COP and IPF.