Yano T, Deterding R R, Simonet W S, Shannon J M, Mason R J
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Am J Respir Cell Mol Biol. 1996 Oct;15(4):433-42. doi: 10.1165/ajrcmb.15.4.8879176.
Acid aspiration is a serious complication of anesthesia and other forms of unconsciousness that can result in the adult respiratory distress syndrome (ARDS), which continues to have a very high mortality despite our current therapeutic interventions. This type of injury damages the alveolar epithelium, principally alveolar type I cells, and requires proliferation of alveolar type II cells to restore gas exchange units. Since keratinocyte growth factor (KGF) has been shown to be a potent mitogen for alveolar type II cells, we evaluated whether intrabronchial administration of KGF would minimize lung injury due to the unilateral instillation of 0.1 N hydrochloric acid (HCl). Rats were pretreated or post-treated by intrabronchial instillation of KGF (5 mg/kg) into the left lung before HCl instillation. All rats receiving KGF at 48 or 72 h before HCl instillation survived for the 7-day observation period, whereas the mortality rate for those receiving HCl alone or saline followed by HCl was 31% and 33%, respectively. Pretreatment with KGF at 72 h but not at 24 or 48 h considerably ameliorated morphologic damage produced by HCl. Inflammatory cells in bronchoalveolar lavage were markedly decreased 3 and 7 days after HCl instillation by the 72-h KGF pretreatment. Pretreatment with KGF at 72 h also attenuated the reduction of total lung capacity, decreased the alpha 1(I) procollagen mRNA levels, and diminished hydroxyproline accumulation due to HCl instillation. Saline pretreatment at 72 h had no significant effect on the HCl injury and subsequent physiologic abnormalities. Our attempts to improve outcome with post-treatment instillation of KGF were unsuccessful. We conclude that KGF pretreatment reduces lung injury due to acid instillation and can prevent subsequent pulmonary fibrosis.
误吸酸性物质是麻醉及其他形式的意识丧失的一种严重并发症，可导致成人呼吸窘迫综合征（ARDS），尽管我们目前采取了治疗措施，但该综合征的死亡率仍然很高。这种类型的损伤会损害肺泡上皮，主要是I型肺泡细胞，需要II型肺泡细胞增殖以恢复气体交换单位。由于角质形成细胞生长因子（KGF）已被证明是II型肺泡细胞的一种强效促有丝分裂原，我们评估了支气管内给予KGF是否能将因单侧滴注0.1N盐酸（HCl）所致的肺损伤降至最低。在滴注HCl前，通过向大鼠左肺支气管内滴注KGF（5mg/kg）对其进行预处理或后处理。在滴注HCl前48或72小时接受KGF的所有大鼠在7天观察期内存活，而单独接受HCl或先接受生理盐水再接受HCl的大鼠死亡率分别为31%和33%。在72小时而非24或48小时用KGF进行预处理可显著改善HCl所致的形态学损伤。72小时KGF预处理使HCl滴注后3天和7天支气管肺泡灌洗中的炎性细胞明显减少。72小时用KGF进行预处理还可减轻肺总量的降低，降低α1（I）前胶原mRNA水平，并减少因滴注HCl所致的羟脯氨酸积累。72小时生理盐水预处理对HCl损伤及随后的生理异常无显著影响。我们通过KGF后处理滴注来改善结局的尝试未成功。我们得出结论，KGF预处理可减轻因滴注酸性物质所致的肺损伤，并可预防随后的肺纤维化。
