THE COMPARISON OF A FIBROGENIC AND 2 NONFIBROGENIC DUSTS BY BRONCHOALVEOLAR LAVAGE
THE COMPARISON OF A FIBROGENIC AND 2 NONFIBROGENIC DUSTS BY BRONCHOALVEOLAR LAVAGE
复制标题
DOI：
10.1016/0041-008x(90)90026-q
复制
发表时间：
1990-02-01
影响因子：
3.8
通讯作者：
BELFIORE, KA
中科院分区：
文献类型：
--
作者：
LINDENSCHMIDT, RC;DRISCOLL, KE;BELFIORE, KA
支气管肺泡灌洗液（BALF）的分析似乎是一个敏感的方法来表征肺内的急性炎症反应。然而，需要更多的工作来确定BALF终点的分析是否可以预测慢性反应（即，纤维化）。本研究的目的是比较一种已知的致纤维化剂二氧化硅和两种已知的非致纤维化剂氧化铝和二氧化钛的剂量和时间肺反应。向动物滴注二氧化硅（0、0.2、1.0或5.0 mg/100 g体重）、二氧化钛（1.0或5 mg/100 g体重）、氧化铝（1.0或5.0 mg/100 g体重）或盐水。在滴注后1、7、14、28和63天处死动物（n = 5/组），并通过生化和细胞测定表征BALF。在暴露后60天测定组织学变化。生化结果表明BALF中乳酸脱氢酶（LDH）、β-葡萄糖醛酸苷酶（BG）、N-乙酰氨基葡萄糖苷酶（NAG）和总蛋白（TP）在所有试验材料的较早时间点以剂量相关方式增加，二氧化硅的变化幅度最大。这些参数的时间响应是显着不同的两类材料。在2个月的研究期间，随着时间的推移，对纤维化粉尘的反应稳定增加，而非纤维化粉尘的水平下降至正常值。在细胞变化中，总细胞数、中性粒细胞和淋巴细胞数是肺反应的最敏感标志物。如生化参数所示，细胞对二氧化硅的反应随着时间的推移而增加，而讨厌的灰尘没有。还发现，与吸入研究类似，高剂量的滋扰性粉尘可能导致毒性/炎症。高剂量水平下的这种毒性强调了在比较潜在的纤维化和非纤维化粉尘时选择相关剂量的重要性。总之，二氧化硅给药后在生化（LDH、TP、BG、NAG）和细胞参数（总细胞、中性粒细胞和淋巴细胞）中观察到的持续性和进行性变化与暴露于该材料后发生的纤维化反应相关。在氧化铝和二氧化钛中观察到的不太显著和短暂的变化与这些讨厌的粉尘的惰性性质有关。本研究的结果表明，BALF的评价可以提供一种预测材料的慢性肺反应的方法。
Analysis of bronchoalveolar lavage fluid (BALF) appears to be a sensitive approach to characterizing an acute inflammatory response within the lung. More work, however, is needed to determine if analyses of BALF endpoints can predict chronic responses (i.e., fibrosis). The objective of the present study was to compare the dose and temporal pulmonary response of a known fibrogenic agent, silica, and two known nonfibrogenic agents, aluminum oxide and titanium dioxide. Animals wee instilled with silica (0, 0.2, 1.0, or 5.0 mg/100 g body wt), titanium dioxide (1.0 or 5 mg/100 g body wt), aluminum oxide (1.0 or 5.0 mg/100 g body wt) or saline. Animals (n = 5/group) were terminated 1, 7, 14, 28, and 63 days following instillation, and the BALF was characterized by biochemical and cellular assays. Histopathological changes were determined at 60 days after exposure. The biochemical results demonstrated BALF levels of lactate dehydrogenase (LDH), .beta.-glucuronidase (BG), N-acetylglucosaminidase (NAG), and total protein (TP) increased in a dose-related fashion at the earlier time points for all tests materials, with the magnitude of change being greatest for silica. The temporal response for these parameters was significantly different for the two classes of materials. With time, the response for the fibrogenic dust steadily increased, while the levels for the nonfibrogenic dusts decreased toward normal values during the 2-month study period. Of the cellular changes, total cell numbers, neutrophils, and lymphocyte numbers were the most sensitive markers of the pulmonary response. As shown with the biochemical parameters, the cellular response to silica increased with time while that of the nuisance dusts did not. It was also found that, similar to inhalation studies, high doses of a nuisance dust may result in toxicity/inflammation. This toxicity at high dose levels emphasizes the importance of choosing relevant doses when comparing potentially fibrogenic and nonfibrogenic dusts. In conclusion, the persistent and progressive changes seen in the biochemical (LDH, TP, BG, NAG) and cellular parameters (total cells, neutrophils and lymphocytes) following silica administration correlated with the fibrotic response which occurred after exposure to this material. The less dramatic and transient changes seen with aluminum oxide and titanium dioxide correlated with the inert nature of these nuisance dusts. The results of this study indicate evaluation of BALF may provide a means to predict the chronic pulmonary response to a material.