氧化铍致大鼠肺纤维化及相关指标的动态变化  

Beryllium Oxide-Induced Pulmonary Fibrosis in Rats and Dynamic Changes of Related Indicators

作　　者：王凯[1] 刘志宏[1] 王和静 王瑶[1] 魏丛慧 张娜[1] 周慈[1] 

机构地区：[1]宁夏医科大学公共卫生与管理学院,宁夏银川750004

出　　处：《环境与职业医学》2016年第7期644-649,共6页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金(编号:81360415)

摘　　要：[目的]探讨氧化铍(Be O)致SD大鼠肺纤维化过程中肺组织的病理变化及纤维化相关指标的动态变化。[方法]无特定病原体(SPF)级SD雄性大鼠64只,随机分为阴性对照组、Be O染毒组。染毒方法采用一次性非暴露式气管内灌注法,Be O染毒组灌注0.5 m L浓度为10 g/L的Be O悬浮液,阴性对照组灌注相同体积的质量分数为0.9%的生理盐水溶液。两组大鼠分别于染毒后的第20、40、60和80天4个时间点处死,每时间点每组各8只。取肺组织制作病理标本通过光学显微镜观察其肺组织病理变化并检测血清和肺组织匀浆中的胶原蛋白Ⅰ(COL-Ⅰ)、胶原蛋白Ⅲ(COL-Ⅲ)、平滑肌肌动蛋白α(α-SMA)、转化生长因子β1(TGF-β1)的表达。[结果]Be O染毒组肺组织病理观察染毒早期主要病理改变为支气管、肺间质炎性细胞浸润,并以单核/巨噬细胞为主,肺泡隔增厚,染毒后期肺泡间隔明显增厚,肺泡腔缩小,部分肺泡结构消失,肺泡结构紊乱,局部可见纤维化结节,结节中央可见Be O粉尘,肺组织局部发生实变。肺组织匀浆中:染毒组中COL-Ⅰ表达高于同时间点的阴性对照组(P<0.05),染毒后60、80天COL-Ⅲ表达高于同时间点阴性对照组(P<0.05),染毒后80天α-SMA表达高于同时间点阴性对照组(P<0.05),染毒后60、80天TGF-β1表达高于同时间点阴性对照组(P<0.05);与染毒后20天时比较,阴性对照组中各指标其他所有时间点与之差异均无统计学意义,染毒后40、60、80天COL-Ⅰ表达高于20天的(P<0.05),染毒后80天α-SMA、COL-Ⅲ、TGF-β1表达高于20天的(P<0.05)。血清中:染毒后60、80天COL-Ⅲ和TGF-β1表达高于同时间点阴性对照组(P<0.05),染毒后80天COL-Ⅰ表达高于同时间点的阴性对照组(P<0.05),染毒组中α-SMA表达均高于同时间点阴性对照组(P<0.05);与20天时比较,阴性对照组中各指标其他所有时间点与之差异均无统计学意义;染毒后60、80天COL-Ⅲ及染毒后80天CO[ Objective ] To study the pulmonary pathological changes and test dynamic changes of lung fibrosis related indicators of SD rats with pulmonary fibrosis induced by beryllium oxide （BeO）. [ Methods ] sixty-four specific pathogen free SD male rats were randomly divided into a negative control group and a BeO exposure group. Using disposable non-exposed intratracheal instillation, the BeO group was injected with lOg/L BeO （0.5 mL）, and the negative control group was injected with 0.9% saline at the same volume. The two groups of rats were respectively neutralized at 20, 40, 60, and 80 d after exposure, eight rats in every batch and each group. Lung tissue specimens were prepared to observe pathological changes under optical microscope and test expression of collagen I （COL-I）, collagen III （COL-llI）, a-smooth muscle actin （c^-SMA）, and transforming growth factor 131 （TGF-131） in lung tissue homogenate and serum. [ Results ] The early pathological changes in lung tissue of the BeO group were located in bronchus, displaying interstitial infiltration of monocytes/macrophages and thickened alveolar septum; while in late stage, it showed obviously thickened alveolar septum, narrowed alveolar space, some alveolus missing and disordered, fibrosis nodules, and BeO dust in the center of nodules, indicating consolidation in part of lung tissues. In the lung tissue homogenate, compared with the negative control group, the COL-I expression level in the exposed group was higher at the same time points （P〈0.05）; the COL-Ill in the exposed group was higher at 60d and 80d （P〈0.05）; the ct-SMA in the exposed group was higher at 80d （P〈0.05）; the TGF-I31 in the exposed group was higher at 60d and 80d （P〈0.05）. Compared with 20d, there were no significant differences in all indices at other time points of the negative control group; the COL- I in the exposed group at 40d, 60d, and 80d was higher （P〈 0.05）; the α-SMA, COL-Ⅲ, and TGF-β1 in the exposed group at 80d were higher �

关 键 词：氧化铍 肺纤维化 胶原蛋白Ⅰ 胶原蛋白Ⅲ Α-平滑肌肌动蛋白 转化生长因子Β1 

分 类 号：R114[医药卫生—卫生毒理学]