Boudreau J, Nadeau D
Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Québec, Canada.
J Toxicol Environ Health. 1987;22(3):329-40. doi: 10.1080/15287398709531075.
In order to evaluate the early response of the alveolar epithelium following lung injury, male Long-Evans adult rats (280-350 g) were treated with a single dose (30 mg/kg, ip) of the herbicide paraquat. No animal died during the 72 h that followed the acute administration of the herbicide. When compared to control, total lipid, phosphatidylcholine, and disaturated phosphatidylcholine contents of lung homogenates from the paraquat-treated rats were significantly reduced 48 h postdose (respectively 10, 24, and 37%). Comparatively, the total lung alkaline phosphatase activity was significantly reduced as early as 12 h postdose, and by 48 h the activity had decreased by approximately 50%. Although a significant decrease in total lung acid phosphatase activity was observed 24 and 48 h after the treatment, the effect was much less than with the alkaline phosphatase activity (15% versus 50%, respectively). The lysosomal beta-N-acetylglucosaminidase and the cytoplasmic lactate dehydrogenase activities were not affected by the herbicide treatment. A subcellular fractionation of the treated lungs showed that 48 h postdose, the total alkaline phosphatase activities associated with lamellar body and surfactant fractions were decreased respectively by 60% and 49%. Due to the intrinsic association of a strong alkaline phosphatase activity with the pulmonary surfactant system, these data suggest that the monitoring of the alkaline phosphatase activity in lung fractions could represent an early and sensitive indicator of toxicity to the alveolar epithelium, most probably to type II cells.
为了评估肺损伤后肺泡上皮的早期反应，选用成年雄性Long-Evans大鼠（280 - 350 g），单次腹腔注射除草剂百草枯（30 mg/kg）。在急性给予除草剂后的72小时内无动物死亡。与对照组相比，百草枯处理组大鼠肺匀浆中总脂质、磷脂酰胆碱和二饱和磷脂酰胆碱含量在给药后48小时显著降低（分别降低10%、24%和37%）。相比之下，肺总碱性磷酸酶活性早在给药后12小时就显著降低，至48小时时活性降低了约50%。虽然在处理后24小时和48小时观察到肺总酸性磷酸酶活性显著降低，但该效应远小于碱性磷酸酶活性（分别为15%和50%）。溶酶体β-N-乙酰氨基葡萄糖苷酶和细胞质乳酸脱氢酶活性不受除草剂处理的影响。对处理后的肺进行亚细胞分级分离显示，给药后48小时，与板层小体和表面活性物质组分相关的总碱性磷酸酶活性分别降低了60%和49%。由于强碱性磷酸酶活性与肺表面活性物质系统存在内在联系，这些数据表明监测肺组分中的碱性磷酸酶活性可能是肺泡上皮，很可能是II型细胞毒性的早期敏感指标。
