Effects Of Epidermal Growth Factor On Alveolar Epithelial Type â…¡ Cells In Rats With Smoke Inhalation Injury

Objective: Alveolar epithelial type II cells (AT II) effect edema clearance by transporting Na+ and liquid out of the air spaces. Active Na+ transport by Na+-K+-ATPase, which is located in the basement membrance, is an important element to help clear lung edema. We hypothesised that growth factors, such as epidermal growth factor, may promote the active repair process of alveolar epithelial cells, and enhance the transalveolar liquid transport after smoke inhalation injury.Methods: 160 Sprague-Dawley rats weighting 160-180g were randomly divided into four groups: group I normal control (n=10); group II (n=50): intratracheal EGF administration; group III(n=50), smoke inhalation; and group IV(n=50): smoke inhalation + intratracheal EGF admininstration. The animals in group II > III and IV were sacrificed at 24, 48, 72, 120 and 168h after smoke inhalation injury and EGF instillation. EGF (100 ug/kg) was instilled into the tracheas with a special needle in the rats of group II and group IV . Alveolar liquid clearance (ALC) was measured with the 125I-albumin method. Anti-SP-A and anti-BrdU immunohistochemical staining were employed to evaluate SP-A secretion and proliferation of AT II. RT-PCR was also employed to detect the mRNA expression of Na+-K+-ATPase a1[ subunit and SP-A in ATII, which were cultured and stimulated with EGF. Results: ALC in group I was measured to be (22.07+3.67)%. Afterinstillation of EGF, it significantly increased to (43.37+11.04)% at 48h (P<0.01), (41.75 + 7.02)% at 72h (P<0.01), and (35.86?.09)% at 120h (P<0.05), respectively, and tended to lower to baseline level at 168h. Smoke inhalation resulted in a decrease by 36.7% in ALC level in the first 24h, and continued to be lowered in the following timepoints. Intratracheal administration of EGF significantly increased ALC to (25.25 + 3.66)%, which was close to the baseline level, at 48h after EGF instillation. Morphological studies found that there was distinct proliferation of AT II cells and increased SP-A secretion in group IV than III. In vitro it was found that SP-A mRNA expression was upregulated by EGF, while the mRNA expression of Na+-K+-ATPase a 1 subunit show no response to EGF stimulating.Conclusion: It was demonstrated that intratracheal instillation of EGF could remarkably enhance the proliferation of AT II, and promote the transalveolar liquid transport in rats with inhalation injury. These results provided evidences that intratracheal instillation of EGF might provide a potential therapeutic strategy for inhalation injury or acute lung injury, in term of enhancing the repair process of alveolar epithelial cells with early recovery of their functions.