矽肺病患者肺泡巨噬细胞死亡受体表达及意义  

Expression and significance of death receptors in alveolar macrophages from silicosis patients

作　　者：姚三巧[1] 陈志远[2] 卢遥 白玉萍[1] 张春民[1] 余艳琴[1] 张喜英[1] 陈刚[2] 张志浩[2] 车审言[2] 徐应军[1] 沈福海[1] 金玉兰[1] 

机构地区：[1]河北联合大学公共卫生学院劳动卫生与环境卫生学科,河北唐山063000 [2]中国煤矿工人北戴河疗养院矽肺科,066104 [3]唐山市工人医院社区医疗部,063000

出　　处：《中国职业医学》2013年第2期91-94,99,共5页China Occupational Medicine

基　　金：国家自然科学基金资助项目(30671741);河北省科技支撑项目(09276196D);中国煤矿尘肺病防治基金项目(煤尘基2005-03)

摘　　要：目的探讨矽肺病患者肺泡巨噬细胞(AM)死亡受体(DR)的表达水平及其与肺纤维化程度的关系。方法以61例进行肺灌洗的汉族男性观察对象及矽肺病患者为观察组,以13例肺部X射线表现完全正常的汉族男性为对照组,分离、纯化及培养各研究对象的AM,检测3种DR[凋亡蛋白-1(Fas)、肿瘤坏死因子受体-1(TNFR1)和肿瘤坏死因子相关凋亡诱导配体受体-2]的表达水平,采用酶联免疫吸附试验检测AM培养上清中的可溶性DR(sDR)水平,采用免疫印迹法检测AM裂解液中3种膜结合型DR(mDR)水平,分析DR表达水平与粉尘接触各因素的关系。结果矽肺病患者膜结合型Fas(mFas)及膜结合型TNFR1(mTNFR1)的相对水平均高于对照组及观察对象(P<0.05),且随着肺部病变的加重而升高;矽肺病患者可溶性Fas(sFas)及可溶性TNFR1(sTNFR1)水平均低于观察对象(P<0.05),且sFas随着肺部病变的加重而下降。结论矽尘诱导的mFas和mTNFR1表达上调、sFas表达下调在矽肺病发病及进展中起重要作用,DR信号通路活化可能是矽肺病发病的重要机制之一。Objective To explore the expression of death receptors （DR） in alveolar macrophages of silicosis patients and the relationship between DR levels and lung fibrosis. Methods Forty-eight male silicosis patients and thirteen male observation objects treated by whole lung lavage were chosen as subjects, Thirteen male health people with normal lung X-ray photograph were selected as the control group, The alveolar macrophags （AM） were collected, purified and incubated at 37 ~C for 24 hours. After 3 kinds of soluble DR （sDR） were determined by ELISA, membrane-bound DR （mDR） were detected by Western blot. The relationships between DR and silica exposure related factors were analyzed. Results The grayscales of mDR in those of the subjects were thicker than those of the controls, and increased with the lung fibrosis progression. The membrane-bound apoptosis related factor 1 （mFas） and membrane-bound tumor necrosis factor reeptor 1 （mTNFR1） levels in silicosis patients were higher than those of the control group and observation objects（P 〈0. 05 ）, and increased with the progression of silicosis. The levels of soluble apoptosis related factor 1 （sFas） and soluble tumor necrosis factor receptor 1 in those of silicosis patients were lower than those of observation objects（ P 〈 0. 05 ）, and sFas decreased with the progression of silicosis. Conclusion The upregulation of mFas and mTNFR1, downregulation of sFas induced by silicon may play an important role in silicosis onset and development. Death receptor signal activation maybe one of the pathophysiological mechanisms of silicosis.

关 键 词：死亡受体 矽肺 凋亡蛋白-1 肿瘤坏死因子受体-1 肿瘤坏死因子相关凋亡诱导配体受体-2 

分 类 号：R135.2[医药卫生—劳动卫生]