高迁移率族蛋白B-1和钙粒蛋白在矽肺发病中的作用  

Role of high mobility group protein B-1 and calgranulin on the pathogenesis of silicosis

作　　者：万文娟[1] 曲晨菲 梁圆圆[2] 祝丽丽[1] 李素平[1] 

机构地区：[1]山西医科大学公共卫生学院,山西太原030001 [2]青岛滨海学院医学院,山东青岛266000

出　　处：《中国工业医学杂志》2014年第2期90-92,F0003,共4页Chinese Journal of Industrial Medicine

摘　　要：目的探讨高迁移率族蛋白B-1（HMGB1）和钙粒蛋白（S100）在矽肺发病中的作用，为充分认识炎症在其中的地位提供新的理论依据。方法选C56BL／6小鼠48只，分为6组：对照组及3、7、14、21、42天实验组，每组8只。进行支气管染矽尘，染尘浓度为200mg／kg。在不同的观察时间处死动物，收集支气管灌洗液，离心后沉淀用于细胞计数。上清液用于检测HMGB1、S100和肿瘤坏死因子-a（TNF-a）。分离肺组织，取右肺用Westernblot检测RAGE。左肺做病理切片，光镜下观察肺组织的病理改变。结果（1）支气管灌洗液中巨噬细胞和中性粒细胞在3d和21d时表现最高，与7、14、42d比较差异有统计学意义（P〈0．05）。（2）HMGB1和S100在染尘3—21d时逐渐增高且具有时间效应关系（P〈0．05），42d时有所降低。（3）TNF—a在3～14d染尘时逐渐降低，21d又升高，42d时明显下降，且各时段间差异有统计学意义（P〈0．05）。（4）RAGE表达水平随观察时间的延长明显降低，并具有时间效应关系（P〈0．05）。（5）随着观察时段的延长，肺泡壁增厚，结构明显破坏，肺泡腔逐渐融合，肺组织炎性病灶增多，在42d时形成了大量的纤维化，几乎看不清肺泡结构。结论HMGB1和钙粒蛋白可能参与矽肺晚期炎症的形成，其生物学效应的发挥不依赖RAGE受体。Objective To explore the role of high mobility group protein （HMG） and calgranulin （S100 protein） on the pathogenesis of silicosis, thereby provide a new theoretical basis for understanding the position of inflammation in it. Methods C56BL/6 mice were randomly divided to 6 groups： control group and different observation time （3, 7, 14, 21 and 42 days） groups, eight mice for each group. Silica dusts were given by bronchial instillation method, the silica suspension concentration was 200 mg/kg （ in 0.9% saline）. The mice were killed at a regular period, collect the bronchial lavage fluids and count cell number in centrifugal precipitate, while the supernatant fluid was used for detection of HMGB1 and TNF alpha. The right lung was used for detecting the content of RAGE with the method of Western blot and the left lungs were prepared for the observation of pathological changes. Results （ 1 ） The neutrophils at 3rd and 21st day after silica-exposure showed the highest values compared with the 7th, 14th, 42nd day. The differences were statistically significant （ P 〈 0.05 ） ; （ 2 ） HMGB1 and S100 protein were increased gradually during the period between 3rd to 21st days （ P 〈 0. 05 ）, but fell at 42nd day ; （ 3 ） TNF-a showed gradually reduced after silica＂ exposure, until the 21st day, but was decreased again at the 42nd day （P 〈 0. 05 ） ; （4） The RAGE expression levels decreased obviously with the time after silica exposure （ P 〈 0. 05 ） ; （5） With the growing of time after silica exposure, the alveolar walls were thickened, the structure was damaged obviously, the alveolar cavity also gradually merged, the inflammation lesions increased, and the fibrosis were so much in lung tissues at the 42nd day that there was nearly no alveolar structure could be seen at that time. Conclusion HMGB1 and S100 protein may participate in the inflammation process of silicosis, and its biological effects do not depended on the RAGE.

关 键 词：矽肺 晚期糖基化终末产物受体(RAGE) 高迁移率族蛋白B-1(HMGB1) 钙粒蛋白(S100 protein) 肿瘤坏死因子-a(TNF-a) 

分 类 号：R994[医药卫生—毒理学]