Deterding R R, Havill A M, Yano T, Middleton S C, Jacoby C R, Shannon J M, Simonet W S, Mason R J
Department of Pediatrics, University of Colorado, Children's Hospital, Denver, USA.
Proc Assoc Am Physicians. 1997 May;109(3):254-68.
Intratracheal instillation of bleomycin produces pulmonary fibrosis in rats. Alveolar type II cell proliferation is thought to minimize the fibrotic response after lung injury. Because keratinocyte growth factor (KGF) stimulates type II cell proliferation in the rat, we designed experiments to evaluate whether intratracheal KGF before or after intratracheal bleomycin would prevent pulmonary fibrosis. Intratracheal bleomycin without KGF resulted in moderate to severe lung injury and subsequent fibrosis. Conversely, intratracheal KGF pretreatment at 48 or 72 hr before bleomycin resulted in minimal to no visible lung injury. Rats pretreated with phosphate buffered saline before bleomycin had significantly more neutrophils and protein in bronchoalveolar lavage fluid at 4 and 6 days and higher hydroxyproline levels after bleomycin as compared to KGF-pretreated rats. Pretreatment with KGF at 48 hr protected against bleomycin-induced alterations in pulmonary physiology and increased surfactant protein C-positive (SP-C)-positive cells and SP-A, SP-B, SP-C, and SP-D mRNA levels after bleomycin instillation when compared to saline pretreated rats on day 1 or day 7. KGF posttreatment protocols did not prevent bleomycin lung injury and fibrosis. We conclude that KGF pretreatment attenuates bleomycin lung injury and increases type II cell proliferation and surfactant protein gene expression after bleomycin instillation in the rat.
气管内注入博来霉素可导致大鼠肺纤维化。肺泡II型细胞增殖被认为可将肺损伤后的纤维化反应降至最低。由于角质形成细胞生长因子（KGF）可刺激大鼠II型细胞增殖，我们设计了实验来评估在气管内注入博来霉素之前或之后给予气管内KGF是否能预防肺纤维化。未给予KGF的气管内博来霉素导致中度至重度肺损伤及随后的纤维化。相反，在博来霉素给药前48或72小时进行气管内KGF预处理导致极少或无明显肺损伤。与KGF预处理的大鼠相比，在博来霉素给药前用磷酸盐缓冲盐水预处理的大鼠在第4天和第6天支气管肺泡灌洗液中的中性粒细胞和蛋白质明显更多，且在博来霉素给药后羟脯氨酸水平更高。与第1天或第7天用盐水预处理的大鼠相比，在48小时用KGF预处理可防止博来霉素诱导的肺生理改变，并增加博来霉素注入后表面活性蛋白C阳性（SP-C）细胞以及SP-A、SP-B、SP-C和SP-D mRNA水平。KGF后处理方案未能预防博来霉素肺损伤和纤维化。我们得出结论，KGF预处理可减轻博来霉素肺损伤，并增加大鼠在博来霉素注入后II型细胞增殖和表面活性蛋白基因表达。
