基于多次非暴露式气管滴注的染毒法研究温石棉致大鼠肺损伤的作用

发布时间：2018-12-19 17:48

【摘要】：温石棉是一种安全性存在争议的石棉,合理可行并且能够真实反映其暴露致病过程的染毒方法对深入研究其致病机理有着重要意义。本文采用多次非暴露式气管滴注的染毒方法对雄性Wistar大鼠分别进行不同浓度温石棉悬液的染毒,在染毒1、3和6个月后记录体重和肺脏器系数,观察肺组织大体及苏木素-伊红(HE)染色的病理形态,对支气管肺泡灌洗液(BALF)中白细胞总数进行分类计数,并测定总蛋白(TP)、乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)和碱性磷酸酶(AKP)的含量。结果表明,多次滴注的方式大鼠死亡率较低,并且每次滴注后能够苏醒的大鼠没有死亡发生;随着四川新康温石棉染毒时间的延长和染毒剂量增加,大鼠体重增长缓慢,肺脏器系数升高,肺大体出现水肿、肉芽肿、萎缩实质化,HE染色观察则表现为炎性细胞增多、肺泡结构遭到破坏以及出现纤维化;随着染毒时间的延长,支气管肺泡灌洗液(BALF)中的白细胞总数、中性粒细胞和淋巴细胞百分比呈上升趋势,巨噬细胞百分比呈下降趋势,TP、LDH、ACP和AKP均表现为上升的趋势,并呈现一定的剂量-效应关系。综上所述,多次非暴露式气管滴注方法可用于模拟温石棉慢性暴露的致病过程,四川新康温石棉可以通过破坏巨噬细胞、肺泡上皮细胞及肺泡上皮-毛细血管屏障造成大鼠的肺损伤。
[Abstract]:Chrysotile asbestos is a kind of asbestos with controversial safety. It is of great significance to study the pathogenic mechanism of chrysotile asbestos which is reasonable and feasible and can truly reflect the pathogenicity of chrysotile asbestos. The male Wistar rats were exposed to different concentrations of chrysotile suspension by repeated unexposed tracheal drip. The body weight and lung organ coefficient were recorded after exposure for 1 and 6 months. The gross lung tissue and histopathology of hematoxylin eosin (HE) staining were observed. The total number of white blood cells in bronchoalveolar lavage fluid (BALF) was counted and the total protein (TP), lactate dehydrogenase (LDH),) was measured. The contents of acid phosphatase (ACP) and alkaline phosphatase (AKP). The results showed that the mortality rate of rats with multiple dripping was lower, and no death occurred in the rats that could wake up after each infusion. With the prolongation of the exposure time and the increase of the dose, the weight of the rats increased slowly, the lung organ coefficient increased, the lung appeared edema, granuloma, atrophy and parenchyma, and the HE staining showed that the inflammatory cells increased. The alveolar structure was destroyed and fibrosis occurred. With the prolongation of exposure time, the total number of leukocytes, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) increased, while the percentage of macrophages decreased. TP,LDH, Both ACP and AKP showed an upward trend and showed a dose-effect relationship. In conclusion, multiple unexposed trachea drip method can be used to simulate the pathogenesis of chronic exposure to chrysotile asbestos. Alveolar epithelial cells and alveolar epithelium-capillary barrier caused lung injury in rats.
【作者单位】：西南医科大学公共卫生学院;西南科技大学;四川绵阳四0四医院检验科;
【基金】：国家自然科学基金面上项目(41472046) 四川省科技厅自然科学基金(14JC0126) 西南医科大学基金资助计划(2015-YJ124)~~
【分类号】：R114

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