Adach Kenji, Suzuki Masami, Sugimoto Tetsurou, Suzuki Shigeo, Niki Rikio, Oyama Atsushi, Uetsuka Koji, Nakamaya Hiroyuki, Doi Kunio
Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, Shizuoka, Japan.
Exp Toxicol Pathol. 2002 Feb;53(6):501-10. doi: 10.1078/0940-2993-00218.
We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on lung injury induced by intratracheal administration of bleomycin (BLM, 2 mg/200 micro1) in rats. In experiment 1, G-CSF (10, 30 and 100 microg/kg/day, s.c.) was administered to rats treated with BLM or saline for 7 days starting immediately after BLM administration. In rats receiving G-CSF alone, a large number of neutrophils were noted in the pulmonary capillaries, although there were no lung lesions. In rats receiving BLM alone, diffuse alveolar damage was observed. The administration of G-CSF to BLM-treated rats increased the total lung lesion per unit of pulmonary parenchyma (total lung lesion %) along with increases in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion in a dose-dependent fashion. In experiment 2, 100 microg/kg/day of G-CSF was administered to rats treated with BLM or saline for up to 28 days starting immediately after BLM administration. The administration of 100 microg/kg/day of G-CSF to BLM-treated rats showed no effects at 14 days but it increased the lung lesion % and the score of lung fibrosis along with the increase in the number of neutrophils infiltrating in the pulmonary lesion at 28 days. These findings suggest that G-CSF administration to BLM-treated rats influenced and exacerbated the BLM-induced acute lung injury, and also exacerbated pulmonary fibrosis in a dose-dependent fashion. The exacerbation of lung injury coincided with the marked increase in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion.
我们研究了粒细胞集落刺激因子（G-CSF）对气管内注射博来霉素（BLM，2mg/200μl）诱导的大鼠肺损伤的影响。在实验1中，于BLM给药后立即开始，对接受BLM或生理盐水处理的大鼠皮下注射G-CSF（10、30和100μg/kg/天），持续7天。在单独接受G-CSF的大鼠中，尽管没有肺部病变，但在肺毛细血管中发现了大量中性粒细胞。在单独接受BLM的大鼠中，观察到弥漫性肺泡损伤。对接受BLM处理的大鼠给予G-CSF，以剂量依赖的方式增加了单位肺实质的总肺损伤（总肺损伤%），同时外周中性粒细胞计数和肺损伤中浸润的中性粒细胞数量也增加。在实验2中，于BLM给药后立即开始，对接受BLM或生理盐水处理的大鼠皮下注射100μg/kg/天的G-CSF，持续28天。对接受BLM处理的大鼠给予100μg/kg/天的G-CSF，在14天时无影响，但在28天时增加了肺损伤%和肺纤维化评分，同时肺损伤中浸润的中性粒细胞数量增加。这些发现表明，对接受BLM处理的大鼠给予G-CSF会影响并加重BLM诱导的急性肺损伤，并且还会以剂量依赖的方式加重肺纤维化。肺损伤的加重与外周中性粒细胞计数和肺损伤中浸润的中性粒细胞数量的显著增加相一致。
