Alveolar epithelial cells and repair ater lung injury

1.肺泡II型细胞的生长因子对肺损伤的影响：我们已经证明角质形成细胞生长因子（KGF）是肺泡II型细胞增殖和分化的有效因子（Am J Physiol 269，1995）。我们已经研究了KGF是否会预防博莱霉素诱导的肺损伤和纤维化。重组人KGF（rhKGF）分别于博莱霉素注射前48 h和注射后24 h行气管内注射。KGF治疗防止了博莱霉素诱导的大鼠肺中1）体重减轻，2）总肺容量降低，3）I型和III型胶原及其mRNA的积累，以及4）表面活性蛋白A（SP-A）、SP-B和SP-C mRNA的放射自显影银颗粒减少。KGF在酸（0.1N HCl）滴注前72小时预处理也可预防酸滴注所致的肺损伤，但后处理无效。2. KGF与人工肺表面活性物质联合治疗后对肺损伤的影响：博莱霉素或酸后48 h联合应用KGF与人工肺表面活性物质，由于肺水肿较重，对肺损伤影响不大。因此，我们正在研究预防肺损伤的最佳滴注时间点。3.预防肺内滴注培养的肺泡细胞引起的肺损伤：我们正在进行KGF刺激培养的肺泡上皮细胞是否能预防肺损伤和纤维化的实验。4.未来计划：我们将研究腺病毒介导的KGF基因转染对肺损伤和肺纤维化的预防作用。

1. Effect of growth factor for alveolar type II cells on lung injury : We have demonstrated that keratinocyte growth factor (KGF) is a potent factor for proliferation and differentiation of alveolar type II cells (Am J Physiol 269,1995). We have examined whether KGF would prevent bleomycin-induced lung injury and fibrosis. Recombinant human KGF (rhKGF) was injected intratracheally at 48h before and 24h after bleomycin. KGF treatment prevents 1) loss of body weight, 2) reduced total lung capacity, 3) accumulation of collagen type I & III and thier mRNAs, and 4) decreased autoradiographic silver grains for surfactant protein A (SP-A), SP-B and SP-C mRNAs in the rat lungs, induced by bleomycin. Lung injury due to acid instillation was also prevented by KGF pretreatment at 72h before acid (0.1N HCl) instillation, but not by posttreatment. 2. Combined posttreatmental effects of KGF and artificial surfactant on lung injury : The combined instillations of KGF and artificial surfactant 48h after bleomycin or acid didn't change lung injury so much because of the strong pulmonary edema. Therefore, we were examining the better time point of instillation for preventing lung injury. 3. Prevention of lung injury due to intratracheal instillation of cultured alveolar cells : we are under experiments on whether cultured alveolar epithelial cells stimulated by KGF would prevent lung injury and fibrosis. 4. Future project : We are going to study gene transfer of KGF using adeno-virus intratracheally for preventing lung injury and fibrosis.