Alveolar epithelial cells and repair ater lung injury

1.肺泡II型细胞生长因子在肺损伤中的作用：我们已证实角质形成细胞生长因子(KGF)是促进肺泡II型细胞增殖和分化的有效因子(Am J Physiol269,1995)。我们研究了KGF是否可以预防博莱霉素所致的肺损伤和纤维化。分别于给药前48h和给药后48h气管内注射重组人KGF(RhKGF)。KGF治疗可防止博莱霉素诱导的大鼠体重减轻，2)总肺活量减少，3)I型和III型胶原及其mRNAs的积聚，以及4)肺表面活性蛋白A(SP-A)、SP-B和SP-CmRNAs的放射自显影银粒减少。KGF在酸(0.1NHCl)滴注前72小时预处理也可预防酸滴注所致的肺损伤，但不能预防后处理。2.联合应用KGF和人工表面活性物质对肺损伤的后处理作用：博莱霉素或酸化后48h联合应用KGF和人工表面活性物质对肺损伤的影响不大，原因是肺水肿大。因此，我们正在研究预防肺损伤的较佳滴注时间点。3.肺泡灌洗致肺损伤的预防：KGF刺激培养的肺泡上皮细胞能否预防肺损伤和肺纤维化的实验正在进行中。4.下一步工作：通过气管内腺病毒转导KGF基因预防肺损伤和纤维化的研究。

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.