尘肺患者肺泡巨噬细胞凋亡及其死亡信号调控机制研究  

Apoptosis of alveolar macrophages in patients with pneumoconiosis and its death signal regulatory mechanisms

作　　者：余艳琴[1,2] 姚三巧[1,2] 白玉萍[1,2] 张春民[1,2] 沈福海[1,2] 徐应军[1,2] 陈志远[3] 陈刚[3] 张志浩[3] 马国宣[3] 黄京慧[3] 车审言[3] 

机构地区：[1]华北煤炭医学院劳动卫生与环境卫生学学科,河北唐山063000 [2]河北省煤矿卫生与安全实验室,063000 [3]中国煤矿工人北戴河疗养院尘肺科,秦皇岛066000

出　　处：《中国职业医学》2010年第2期99-103,共5页China Occupational Medicine

基　　金：国家自然科学基金资助项目(30671741)

摘　　要：目的初步研究尘肺患者肺泡巨噬细胞(AM)的凋亡情况以及肿瘤坏死因子-α及其受体(TNF-α/TNFR)信号通路对AM凋亡的调控作用,为尘肺病的早期防治提供依据。方法选取30例尘肺患者为研究对象,收集其肺泡灌洗回收液,分离纯化AM,将实验分为5组,即未处理组、超氧化物歧化酶(SOD)组、TNF-α/TNFR组、抗-TNF-α组、半胱氨酰天冬氨酸特异蛋白(Caspase)-8抑制剂组。培养24h后,收获AM,分别用光学显微镜、透射电子显微镜、荧光共聚焦显微镜检测AM凋亡的情况。采用SAS8.2软件进行方差分析和2分析。结果光学显微镜、荧光共聚焦显微镜、透射电镜下均可见凋亡细胞染色质浓缩、边缘化、染色质分割成块状、核膜不完整和凋亡小体等典型的凋亡形态。SOD组、抗-TNF-α组、Caspase-8抑制剂组的AM凋亡指数均低于未处理组。结论尘肺患者AM存在一定程度的凋亡,表现为形态学的改变,凋亡程度与接尘性质有关,与尘肺期别、接尘工龄、脱尘年限无关。SOD复合酶、抗-TNF-α抗体、Caspase-8抑制剂可在信号通路的不同环节阻断信号转导,抑制AM凋亡的发生。Objective To study preliminarily apoptosis of alveolar macrophages （AM） and tumor necrosis factor,as well as receptor （TNF-α/TNFR） signaling pathway of apoptosis of AM in the patients with pneumoconiosis,in order to provide some basis for prevention and treatment of pneumoconiosis.Methods 30 pneumoconiosis patients were chosen as subjects.AM obtained from the massive whole lung lavage fluid were purified and divided into 5 groups：untreated group,SOD group,TNF-α/TNFR group,anti-TNF-α group and Caspase-8 inhibitor Group.Cultured for 24 h,AM were harvested,and the apoptotic character was observed under light microscope,transmission electron microscope and fluorescence confocal microscope.SAS 8.2 software was used to analyze the difference between or among groups.Results Apoptosis AM showed typical morphological changes under the microscopes.There were no significant differences of apoptotic indexes among different ages,length of service,property of dust,beginning age exposed to dust.The apoptosis indexes in SOD group,anti TNF-α group,Caspase-8 inhibitor group of AM were lower than that of the untreated group.Conclusion Some apoptotic AM were found in pneumoconiosis patients,showing apoptotic characters of morphological changes.No significant differences among stages of pneumoconiosis were observed.SOD enzyme,anti-TNF-α antibody,Caspase-8 inhibitors might block signal transduction and inhibite the occurrence of apoptosis of AM.

关 键 词：尘肺 肺泡巨噬细胞 凋亡 TNF-α/TNFR信号通路 

分 类 号：R37[医药卫生—病原生物学]