长期吸入糖皮质激素对慢性阻塞性肺疾病患者诱导痰Toll样受体2表达的影响  

Influence of long-term use of inhaled corticosteroid on Toll like receptor 2 expression in induced sputum in severe chronic obstructive pulmonary disease patients

作　　者：朱海星[1,2] 施宇衡[3] 汤葳[1] 时国朝[1] 万欢英[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院呼吸科,上海200025 [2]复旦大学附属中山医院呼吸科,上海200032 [3]上海交通大学医学院附属第三人民医院呼吸科,上海201999

出　　处：《内科理论与实践》2013年第6期427-430,共4页Journal of Internal Medicine Concepts & Practice

摘　　要：目的:评价长期吸入糖皮质激素的治疗对重度慢性阻塞性肺疾病(COPD)患者诱导痰巨噬细胞Toll样受体2(TLR2)的表达是否产生影响。方法:收集2010年3月到2011年8月上海交通大学医学院附属瑞金医院呼吸科门诊就诊的有长期吸烟史的男性稳定期重度COPD患者,根据是否长期使用吸入型激素(≥500μg/d丙酸氟替卡松,疗程≥1年)分为使用吸入激素组和未使用吸入激素组。通过流式细胞检测技术测定2组患者诱导痰巨噬细胞表面和细胞内TLR2的表达,并将痰细胞抽提mRNA转录cDNA后进行实时定量PCR检测,检测TLR2和肿瘤坏死因子(TNF)αmRNA的表达情况。比较2组间的差异。结果:诱导痰巨噬细胞细胞表面TLR2的表达在规律使用吸入激素组显著低于未用吸入激素组(5.35±1.67比12.81±4.89,P=0.019)。实时定量PCR检测TLR2 mRNA、炎症介质TNF-αmRNA水平在2组患者间的差异无显著意义。而TLR2细胞内与细胞表面表达水平之间(r=0.654,P=0.017),TNF-αmRNA与TLR2细胞表面蛋白表达水平之间(r=0.716,P=0.012)均有显著相关性。结论:长期吸入糖皮质激素治疗重度COPD可能会导致呼吸道局部TLR2的表达下降,这可能是患者局部抗感染免疫降低的原因之一。Objective To evaluate the influence of long-term use of inhaled corticosteroid on Toll like receptor 2 （TLR2）expression on and in macrophages from induced sputum in severe chronic obstructive pulmonary disease （COPD） patients. Methods Severe smoking stable COPD male patients treated in COPD out patient department were divided into two groups： long-term inhaled corticosteroid（ICS） treatment group （ICS ≥ 500 μg/d futieasone propionate, ≥ 1 year） （n=21） and ICS naive group （n=29）. The TLR2 extracellular （surface） and intracellular expression in macrophages from induced sputum were detected by cytometry. The mRNA expressions of TLR2 and tumor necrosis factor （TNF） of in cells from induced sputum were assayed by real-time PCR. Results The TLR2 extraeellular expression on maerophages from induced sputum in long-term ICS treatment group was lower than that in the ICS naive group （5.35±1.67 vs 12.81±4.89, P=0.019）. The TLR2 intracellular expression in macrophages （13.69±1.17 vs 20.12±4.37）, the TLR2 mRNA （3.64±1.61 vs 5.13±1.41） and TNF-α mRNA （6.92±2.23 vs 8.18±1.49） expressions also showed decreased trends in ICS long-term treatment group when compared with ICS naive group but had not reached significant level. There were positive correlations between TLR2 extracellular and TLR2 intracellular expressions （r=0.645, P=0.017）, as well as between TNF-ct mRNA and TLR2 extracellular expressions （r=0.716, P=0.012）. Conclusions Long-term use of ICS may have negative influence on TLR2 expression in airway of COPD patients, which may increase the susceptibility to pulmonary infection in severe COPD patients.

关 键 词：慢性阻塞性肺疾病 TOLL样受体2 诱导痰 

分 类 号：R563.9[医药卫生—呼吸系统]