摘要
目的 探讨中性粒细胞胞外陷阱（NETs）诱导血管内皮细胞损伤在皮肌炎合并肺间质病变（ILD）中的作用.方法 检测健康对照者、皮肌炎患者（包括皮肌炎合并ILD者,皮肌炎未合并ILD者）的血清游离DNA浓度、血清涎液化糖链蛋白（KL-6）水平,分离受试者外周血中性粒细胞,体外用12-豆蔻酸-13-乙酸佛波醇（PMA）刺激获得NETs,用NETs刺激人脐静脉内皮细胞,倒置相差显微镜观察细胞形态,检测人脐静脉内皮细胞存活率来反映NETs对血管内皮细胞的损伤.结果 皮肌炎患者血清游离DNA浓度高于健康对照者[（271.27 ±76.53） μg/L比（152.89 ±37.34） μg/L,P＜0.001],皮肌炎合并ILD者血清游离DNA浓度高于皮肌炎未合并ILD者[（302.67±74.15） μg/L比（235.59 ±63.55）μg/L,P＜0.005];皮肌炎患者血清KL-6水平高于健康对照者[（3.08 ±2.07） μg/L比（0.87 ±0.51） μ.g/L,P＜0.001],皮肌炎合并ILD者血清KL-6水平高于皮肌炎未合并ILD者[（4.00±2.44） μg/L比（2.03 ±0.61） μg/L,P＜0.005].皮肌炎患者血管内皮细胞存活率低于健康对照者[（53±11）％比（70±5）％,P＜0.001];皮肌炎合并ILD者血管内皮细胞存活率低于皮肌炎未合并ILD者[（44±4）％比（61±8）％,P＜0.01].相关分析,血清游离DNA浓度与血清KL-6水平呈正相关（r=0.251,P＜0.05）.结论 NETs对皮肌炎合并ILD的发病有重要作用,可能是一个重要的治疗靶点.
Objective To explore the role of neutrophil extracellular traps （NETs）-induced endothelial cell damage in the pathogenesis of dermatomyositis （DM）-associated interstitial lung disease （ILD）.Methods Serum free DNA and krebs von den lungen-6 （KL-6） level were tested in healthy controls,dermatomyositis patients with or without interstitial lung disease （DM-ILD and DM-NILD）.Subjects＆#39; peripheral blood neutrophils were stimulated with phorbol 12-myristate 13-acetate （PMA）,then human umbilical vein endothelial cells （HUVECs） were co-cultured with NETs.The cell morphology was observed by the inverted phase contrast microscope.Cell viability was detected by cell counting kit-8 （CCK8）.Results The concentration of serum free DNA in DM patients [（271.27 ± 76.53） μg/L] was significantly higher than that in health control （HC） [（152.89 ± 37.34） μg/L,P 〈 0.001].Moreover,free DNA level in DM-ILD patients [（302.67 ± 74.15） μg/L] was higher than that in DM-NILD patients [（235.59 ±63.55） μg/L,P 〈0.005].The concentration of KL-6in DM patients [（3.08 ±2.07） μg/L] was higher than that in HC [（0.87 ± 0.51） μg/L,P 〈 0.001].Similarly,KL-6 in DM-ILD patients [（4.00 ± 2.44） μg/L] was higher than that of DM-NILD patients [（2.03 ± 0.61） μg/L,P 〈 0.005].Free DNA and KL-6 were positively correlated （r =0.251,P 〈 0.05）.The survival of endothelial cells in DM group （53 ± 11） % was lower than that of HC group [（70 ± 5） %,P 〈 0.001].Not surprisingly,the survival of endothelial cells in DM-ILD group （44 ±4） % was lower than that in DM-NILD group [（61 ± 8） %,P 〈 0.01].Conclusion NETs could play an important role in the pathogenesis of dermatomyositis associated interstitial lung disease,suggesting that NETs may be the potential therapeutic target.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2017年第9期650-654,共5页
Chinese Journal of Internal Medicine
基金
国家自然科学基金（81172870）
四川省科技厅国际项目（2014HH0027）
关键词
皮肌炎
中性粒细胞胞外陷阱
肺间质病变
结缔组织病
Dermatomyositis
Neutrophil extracellular traps
Interstitial lung disease
Connective tissue disease
